id sid tid token lemma pos admet-9 1 1 microsoft microsoft PROPN admet-9 1 2 word word NOUN admet-9 1 3 9.doc 9.doc PROPN admet-9 1 4 doi doi NOUN admet-9 1 5 : : PUNCT admet-9 1 6     SPACE admet-9 1 7 10.5599 10.5599 NUM admet-9 1 8 / / SYM admet-9 1 9 admet.1.3.9 admet.1.3.9 NOUN admet-9 1 10     SPACE admet-9 1 11 19 19 NUM admet-9 1 12     SPACE admet-9 1 13 admet admet NOUN admet-9 1 14     SPACE admet-9 1 15 & & CCONJ admet-9 1 16     SPACE admet-9 1 17 dmpk dmpk VERB admet-9 1 18     SPACE admet-9 1 19 1(3 1(3 NUM admet-9 1 20 ) ) PUNCT admet-9 1 21     SPACE admet-9 1 22 ( ( PUNCT admet-9 1 23 2013 2013 NUM admet-9 1 24 ) ) PUNCT admet-9 1 25     SPACE admet-9 1 26 19‐28 19‐28 NUM admet-9 1 27 ; ; PUNCT admet-9 1 28     SPACE admet-9 1 29 doi doi NOUN admet-9 1 30 : : PUNCT admet-9 1 31     SPACE admet-9 1 32 10.5599 10.5599 NUM admet-9 1 33 / / SYM admet-9 1 34 admet.1.3.9 admet.1.3.9 NOUN admet-9 1 35         SPACE admet-9 1 36 open open ADJ admet-9 1 37     SPACE admet-9 1 38 access access NOUN admet-9 1 39     SPACE admet-9 1 40 : : PUNCT admet-9 1 41     SPACE admet-9 1 42 issn issn PROPN admet-9 1 43     SPACE admet-9 1 44 : : PUNCT admet-9 1 45     SPACE admet-9 1 46 1848‐7718 1848‐7718 NUM admet-9 1 47             SPACE admet-9 1 48 perspective perspective NOUN admet-9 1 49     SPACE admet-9 1 50 what what PRON admet-9 1 51     SPACE admet-9 1 52 adme adme NOUN admet-9 1 53     SPACE admet-9 1 54 tests test NOUN admet-9 1 55     SPACE admet-9 1 56 should should AUX admet-9 1 57     SPACE admet-9 1 58 be be AUX admet-9 1 59     SPACE admet-9 1 60 conducted conduct VERB admet-9 1 61     SPACE admet-9 1 62 for for ADP admet-9 1 63     SPACE admet-9 1 64 preclinical preclinical ADJ admet-9 1 65     SPACE admet-9 1 66 studies study NOUN admet-9 1 67 ? ? PUNCT admet-9 1 68     SPACE admet-9 1 69 hong hong PROPN admet-9 1 70     SPACE admet-9 1 71 wan wan PROPN admet-9 1 72     SPACE admet-9 1 73 shanghai shanghai PROPN admet-9 1 74     SPACE admet-9 1 75 hengrui hengrui PROPN admet-9 1 76     SPACE admet-9 1 77 pharmaceutical pharmaceutical PROPN admet-9 1 78     SPACE admet-9 1 79 co. co. PROPN admet-9 1 80 , , PUNCT admet-9 1 81     SPACE admet-9 1 82 ltd ltd PROPN admet-9 1 83 . . PROPN admet-9 1 84         SPACE admet-9 1 85 dept dept PROPN admet-9 1 86 . . PUNCT admet-9 1 87     SPACE admet-9 1 88 of of ADP admet-9 1 89     SPACE admet-9 1 90 dmpk dmpk PROPN admet-9 1 91 / / SYM admet-9 1 92 tox tox NOUN admet-9 1 93 , , PUNCT admet-9 1 94     SPACE admet-9 1 95 shanghai shanghai PROPN admet-9 1 96 , , PUNCT admet-9 1 97     SPACE admet-9 1 98 p.r p.r PROPN admet-9 1 99 . . PROPN admet-9 1 100     SPACE admet-9 1 101 china china PROPN admet-9 1 102     SPACE admet-9 1 103 e‐mail e‐mail PUNCT admet-9 1 104 : : PUNCT admet-9 1 105     SPACE admet-9 1 106 wanh@shhrp.com wanh@shhrp.com VERB admet-9 1 107     SPACE admet-9 1 108 tel tel NOUN admet-9 1 109 : : PUNCT admet-9 1 110     SPACE admet-9 1 111 +86(0)21‐54759066‐1313 +86(0)21‐54759066‐1313 NUM admet-9 1 112 ; ; PUNCT admet-9 1 113     SPACE admet-9 1 114 fax fax NOUN admet-9 1 115 : : PUNCT admet-9 1 116     SPACE admet-9 1 117 +86(0)21‐54759072 +86(0)21‐54759072 NOUN admet-9 1 118 ; ; PUNCT admet-9 1 119     SPACE admet-9 1 120 mobile mobile NOUN admet-9 1 121 : : PUNCT admet-9 1 122     SPACE admet-9 1 123 +86‐18036618308 +86‐18036618308 VERB admet-9 1 124     SPACE admet-9 1 125 received receive VERB admet-9 1 126 : : PUNCT admet-9 1 127     SPACE admet-9 1 128 june june PROPN admet-9 1 129     SPACE admet-9 1 130 06th 06th NOUN admet-9 1 131 , , PUNCT admet-9 1 132     SPACE admet-9 1 133 2013 2013 NUM admet-9 1 134 ; ; PUNCT admet-9 1 135     SPACE admet-9 1 136 revised revise VERB admet-9 1 137 : : PUNCT admet-9 1 138     SPACE admet-9 1 139 july july NOUN admet-9 1 140     SPACE admet-9 1 141 01st 01st NOUN admet-9 1 142 , , PUNCT admet-9 1 143     SPACE admet-9 1 144 2013 2013 NUM admet-9 1 145 ; ; PUNCT admet-9 1 146     SPACE admet-9 1 147 published publish VERB admet-9 1 148 : : PUNCT admet-9 1 149     SPACE admet-9 1 150 july july NOUN admet-9 1 151     SPACE admet-9 1 152 03rd 03rd NOUN admet-9 1 153 , , PUNCT admet-9 1 154     SPACE admet-9 1 155 2013 2013 NUM admet-9 1 156             SPACE admet-9 1 157 abstract abstract NOUN admet-9 1 158     SPACE admet-9 1 159 the the DET admet-9 1 160     SPACE admet-9 1 161 pharmaceutical pharmaceutical NOUN admet-9 1 162     SPACE admet-9 1 163 industry industry NOUN admet-9 1 164     SPACE admet-9 1 165 has have AUX admet-9 1 166     SPACE admet-9 1 167 been be AUX admet-9 1 168     SPACE admet-9 1 169 evolving evolve VERB admet-9 1 170     SPACE admet-9 1 171 in in ADP admet-9 1 172     SPACE admet-9 1 173 recent recent ADJ admet-9 1 174     SPACE admet-9 1 175 years year NOUN admet-9 1 176 , , PUNCT admet-9 1 177     SPACE admet-9 1 178 which which PRON admet-9 1 179     SPACE admet-9 1 180 made make VERB admet-9 1 181     SPACE admet-9 1 182 numerous numerous ADJ admet-9 1 183     SPACE admet-9 1 184 cros cro NOUN admet-9 1 185     SPACE admet-9 1 186 and and CCONJ admet-9 1 187     SPACE admet-9 1 188 biotech biotech NOUN admet-9 1 189     SPACE admet-9 1 190 companies company NOUN admet-9 1 191     SPACE admet-9 1 192 conducting conduct VERB admet-9 1 193     SPACE admet-9 1 194 drug drug NOUN admet-9 1 195     SPACE admet-9 1 196 discovery discovery NOUN admet-9 1 197     SPACE admet-9 1 198 and and CCONJ admet-9 1 199     SPACE admet-9 1 200 development development NOUN admet-9 1 201     SPACE admet-9 1 202 programs program NOUN admet-9 1 203     SPACE admet-9 1 204 and and CCONJ admet-9 1 205     SPACE admet-9 1 206 services service NOUN admet-9 1 207     SPACE admet-9 1 208 in in ADP admet-9 1 209     SPACE admet-9 1 210 china china PROPN admet-9 1 211 . . PUNCT admet-9 1 212     SPACE admet-9 2 1 as as ADP admet-9 2 2     SPACE admet-9 2 3 a a DET admet-9 2 4     SPACE admet-9 2 5 very very ADV admet-9 2 6     SPACE admet-9 2 7 comprehensive comprehensive ADJ admet-9 2 8     SPACE admet-9 2 9 and and CCONJ admet-9 2 10     SPACE admet-9 2 11 important important ADJ admet-9 2 12     SPACE admet-9 2 13 technology technology NOUN admet-9 2 14     SPACE admet-9 2 15 platform platform NOUN admet-9 2 16     SPACE admet-9 2 17 bridging bridging NOUN admet-9 2 18     SPACE admet-9 2 19 efficacy efficacy NOUN admet-9 2 20     SPACE admet-9 2 21 and and CCONJ admet-9 2 22     SPACE admet-9 2 23 safety safety NOUN admet-9 2 24 , , PUNCT admet-9 2 25     SPACE admet-9 2 26 the the DET admet-9 2 27     SPACE admet-9 2 28 dmpk dmpk NOUN admet-9 2 29     SPACE admet-9 2 30 has have AUX admet-9 2 31     SPACE admet-9 2 32 become become VERB admet-9 2 33     SPACE admet-9 2 34 a a DET admet-9 2 35     SPACE admet-9 2 36 mature mature ADJ admet-9 2 37     SPACE admet-9 2 38 discovery discovery NOUN admet-9 2 39     SPACE admet-9 2 40 function function NOUN admet-9 2 41     SPACE admet-9 2 42 to to ADP admet-9 2 43     SPACE admet-9 2 44 optimise optimise VERB admet-9 2 45     SPACE admet-9 2 46 adme adme NOUN admet-9 2 47     SPACE admet-9 2 48 properties property NOUN admet-9 2 49     SPACE admet-9 2 50 in in ADP admet-9 2 51     SPACE admet-9 2 52 drug drug NOUN admet-9 2 53     SPACE admet-9 2 54 design design NOUN admet-9 2 55     SPACE admet-9 2 56 and and CCONJ admet-9 2 57     SPACE admet-9 2 58 screening screening NOUN admet-9 2 59 , , PUNCT admet-9 2 60     SPACE admet-9 2 61 and and CCONJ admet-9 2 62     SPACE admet-9 2 63 dramatically dramatically ADV admet-9 2 64     SPACE admet-9 2 65 mitgate mitgate NOUN admet-9 2 66     SPACE admet-9 2 67 attrition attrition NOUN admet-9 2 68     SPACE admet-9 2 69 rates rate NOUN admet-9 2 70     SPACE admet-9 2 71 during during ADP admet-9 2 72     SPACE admet-9 2 73 the the DET admet-9 2 74     SPACE admet-9 2 75 last last ADJ admet-9 2 76     SPACE admet-9 2 77 decades decade NOUN admet-9 2 78 . . PUNCT admet-9 2 79     SPACE admet-9 3 1 in in ADP admet-9 3 2     SPACE admet-9 3 3 this this DET admet-9 3 4     SPACE admet-9 3 5 article article NOUN admet-9 3 6 , , PUNCT admet-9 3 7     SPACE admet-9 3 8 the the DET admet-9 3 9     SPACE admet-9 3 10 author author NOUN admet-9 3 11     SPACE admet-9 3 12 addresses address NOUN admet-9 3 13     SPACE admet-9 3 14 several several ADJ admet-9 3 15     SPACE admet-9 3 16 frequent frequent ADJ admet-9 3 17     SPACE admet-9 3 18 questions question NOUN admet-9 3 19     SPACE admet-9 3 20 associated associate VERB admet-9 3 21     SPACE admet-9 3 22 with with ADP admet-9 3 23     SPACE admet-9 3 24 adme adme NOUN admet-9 3 25 / / SYM admet-9 3 26 dmpk dmpk NOUN admet-9 3 27     SPACE admet-9 3 28 studies study NOUN admet-9 3 29 , , PUNCT admet-9 3 30     SPACE admet-9 3 31 e.g. e.g. ADV admet-9 3 32 , , PUNCT admet-9 3 33     SPACE admet-9 3 34 what what PRON admet-9 3 35     SPACE admet-9 3 36 adme adme NOUN admet-9 3 37     SPACE admet-9 3 38 tests test NOUN admet-9 3 39     SPACE admet-9 3 40 should should AUX admet-9 3 41     SPACE admet-9 3 42 be be AUX admet-9 3 43     SPACE admet-9 3 44 conducted conduct VERB admet-9 3 45     SPACE admet-9 3 46 for for ADP admet-9 3 47     SPACE admet-9 3 48 preclinical preclinical ADJ admet-9 3 49     SPACE admet-9 3 50 studies study NOUN admet-9 3 51 ? ? PUNCT admet-9 3 52     SPACE admet-9 4 1 what what PRON admet-9 4 2     SPACE admet-9 4 3 should should AUX admet-9 4 4     SPACE admet-9 4 5 a a DET admet-9 4 6     SPACE admet-9 4 7 typical typical ADJ admet-9 4 8     SPACE admet-9 4 9 investigational investigational ADJ admet-9 4 10     SPACE admet-9 4 11 new new ADJ admet-9 4 12     SPACE admet-9 4 13 drug drug NOUN admet-9 4 14     SPACE admet-9 4 15 ( ( PUNCT admet-9 4 16 ind ind NOUN admet-9 4 17 ) ) PUNCT admet-9 4 18     SPACE admet-9 4 19 enabling enable VERB admet-9 4 20     SPACE admet-9 4 21 package package NOUN admet-9 4 22     SPACE admet-9 4 23 cover cover NOUN admet-9 4 24 ? ? PUNCT admet-9 4 25     SPACE admet-9 4 26 which which DET admet-9 4 27     SPACE admet-9 4 28 adme adme NOUN admet-9 4 29 / / SYM admet-9 4 30 dmpk dmpk NOUN admet-9 4 31     SPACE admet-9 4 32 studies study NOUN admet-9 4 33     SPACE admet-9 4 34 require require VERB admet-9 4 35     SPACE admet-9 4 36 good good ADJ admet-9 4 37     SPACE admet-9 4 38 laboratory laboratory NOUN admet-9 4 39     SPACE admet-9 4 40 practice practice NOUN admet-9 4 41     SPACE admet-9 4 42 ( ( PUNCT admet-9 4 43 glp glp PROPN admet-9 4 44 ) ) PUNCT admet-9 4 45     SPACE admet-9 4 46 or or CCONJ admet-9 4 47     SPACE admet-9 4 48 non‐glp non‐glp NOUN admet-9 4 49 ? ? NOUN admet-9 4 50     SPACE admet-9 4 51 what what PRON admet-9 4 52     SPACE admet-9 4 53 does do VERB admet-9 4 54     SPACE admet-9 4 55 a a DET admet-9 4 56     SPACE admet-9 4 57 good good ADJ admet-9 4 58     SPACE admet-9 4 59 pk pk NOUN admet-9 4 60     SPACE admet-9 4 61 profile profile NOUN admet-9 4 62     SPACE admet-9 4 63 look look NOUN admet-9 4 64     SPACE admet-9 4 65 like like ADP admet-9 4 66 ? ? PUNCT admet-9 4 67         SPACE admet-9 4 68 the the DET admet-9 4 69     SPACE admet-9 4 70 author author NOUN admet-9 4 71     SPACE admet-9 4 72 presents present VERB admet-9 4 73     SPACE admet-9 4 74 a a DET admet-9 4 75     SPACE admet-9 4 76 straightforward straightforward ADJ admet-9 4 77     SPACE admet-9 4 78 overview overview NOUN admet-9 4 79     SPACE admet-9 4 80 of of ADP admet-9 4 81     SPACE admet-9 4 82 these these DET admet-9 4 83     SPACE admet-9 4 84 basic basic ADJ admet-9 4 85     SPACE admet-9 4 86 questions question NOUN admet-9 4 87     SPACE admet-9 4 88 from from ADP admet-9 4 89     SPACE admet-9 4 90 his his PRON admet-9 4 91     SPACE admet-9 4 92 many many ADJ admet-9 4 93     SPACE admet-9 4 94 years year NOUN admet-9 4 95 ’ ' PUNCT admet-9 4 96     SPACE admet-9 4 97 experience experience NOUN admet-9 4 98     SPACE admet-9 4 99 in in ADP admet-9 4 100     SPACE admet-9 4 101 both both DET admet-9 4 102     SPACE admet-9 4 103 pharmaceutical pharmaceutical NOUN admet-9 4 104     SPACE admet-9 4 105 research research NOUN admet-9 4 106     SPACE admet-9 4 107 and and CCONJ admet-9 4 108     SPACE admet-9 4 109 cro cro NOUN admet-9 4 110     SPACE admet-9 4 111 in in ADP admet-9 4 112     SPACE admet-9 4 113 supporting support VERB admet-9 4 114     SPACE admet-9 4 115 drug drug NOUN admet-9 4 116     SPACE admet-9 4 117 discovery discovery NOUN admet-9 4 118     SPACE admet-9 4 119 projects project NOUN admet-9 4 120     SPACE admet-9 4 121 and and CCONJ admet-9 4 122     SPACE admet-9 4 123 ind ind NOUN admet-9 4 124     SPACE admet-9 4 125 filing filing NOUN admet-9 4 126 . . PUNCT admet-9 4 127     SPACE admet-9 5 1 keywords keywords AUX admet-9 5 2     SPACE admet-9 5 3 dmpk dmpk NOUN admet-9 5 4 , , PUNCT admet-9 5 5     SPACE admet-9 5 6 pk pk NOUN admet-9 5 7 , , PUNCT admet-9 5 8     SPACE admet-9 5 9 toxicity toxicity NOUN admet-9 5 10 , , PUNCT admet-9 5 11     SPACE admet-9 5 12 safety safety NOUN admet-9 5 13 , , PUNCT admet-9 5 14     SPACE admet-9 5 15 screening screen VERB admet-9 5 16     SPACE admet-9 5 17 cascade cascade NOUN admet-9 5 18 , , PUNCT admet-9 5 19     SPACE admet-9 5 20 metabolite metabolite NOUN admet-9 5 21 , , PUNCT admet-9 5 22     SPACE admet-9 5 23 drug‐drug drug‐drug NOUN admet-9 5 24     SPACE admet-9 5 25 interaction interaction NOUN admet-9 5 26 , , PUNCT admet-9 5 27     SPACE admet-9 5 28 investigational investigational ADJ admet-9 5 29     SPACE admet-9 5 30 new new ADJ admet-9 5 31     SPACE admet-9 5 32 drug drug NOUN admet-9 5 33         SPACE admet-9 5 34 1 1 NUM admet-9 5 35 . . PUNCT admet-9 5 36     SPACE admet-9 6 1 dmpk dmpk NOUN admet-9 6 2 / / SYM admet-9 6 3 adme adme NOUN admet-9 6 4 : : PUNCT admet-9 6 5     SPACE admet-9 6 6 definition definition NOUN admet-9 6 7     SPACE admet-9 6 8 and and CCONJ admet-9 6 9     SPACE admet-9 6 10 study study NOUN admet-9 6 11     SPACE admet-9 6 12 purpose purpose NOUN admet-9 6 13     SPACE admet-9 6 14 dmpk dmpk NOUN admet-9 6 15 , , PUNCT admet-9 6 16     SPACE admet-9 6 17 or or CCONJ admet-9 6 18     SPACE admet-9 6 19 drug drug NOUN admet-9 6 20     SPACE admet-9 6 21 metabolism metabolism NOUN admet-9 6 22     SPACE admet-9 6 23 and and CCONJ admet-9 6 24     SPACE admet-9 6 25 pharmacokinetics pharmacokinetic NOUN admet-9 6 26 , , PUNCT admet-9 6 27     SPACE admet-9 6 28 is be AUX admet-9 6 29     SPACE admet-9 6 30 an an DET admet-9 6 31     SPACE admet-9 6 32 important important ADJ admet-9 6 33     SPACE admet-9 6 34 part part NOUN admet-9 6 35     SPACE admet-9 6 36 of of ADP admet-9 6 37     SPACE admet-9 6 38 studies study NOUN admet-9 6 39     SPACE admet-9 6 40 often often ADV admet-9 6 41     SPACE admet-9 6 42 referred refer VERB admet-9 6 43     SPACE admet-9 6 44 to to ADP admet-9 6 45     SPACE admet-9 6 46 as as ADP admet-9 6 47     SPACE admet-9 6 48 adme adme NOUN admet-9 6 49     SPACE admet-9 6 50 ( ( PUNCT admet-9 6 51 absorption absorption NOUN admet-9 6 52 , , PUNCT admet-9 6 53     SPACE admet-9 6 54 distribution distribution NOUN admet-9 6 55 , , PUNCT admet-9 6 56     SPACE admet-9 6 57 metabolism metabolism NOUN admet-9 6 58 , , PUNCT admet-9 6 59     SPACE admet-9 6 60 and and CCONJ admet-9 6 61     SPACE admet-9 6 62 elimination elimination NOUN admet-9 6 63 ) ) PUNCT admet-9 6 64 . . PUNCT admet-9 6 65         SPACE admet-9 7 1 absorption absorption NOUN admet-9 7 2     SPACE admet-9 7 3 ( ( PUNCT admet-9 7 4 how how SCONJ admet-9 7 5     SPACE admet-9 7 6 much much ADJ admet-9 7 7     SPACE admet-9 7 8 and and CCONJ admet-9 7 9     SPACE admet-9 7 10 how how SCONJ admet-9 7 11     SPACE admet-9 7 12 fast fast VERB admet-9 7 13 , , PUNCT admet-9 7 14     SPACE admet-9 7 15 often often ADV admet-9 7 16     SPACE admet-9 7 17 referred refer VERB admet-9 7 18     SPACE admet-9 7 19 to to ADP admet-9 7 20     SPACE admet-9 7 21 as as ADP admet-9 7 22     SPACE admet-9 7 23 the the DET admet-9 7 24     SPACE admet-9 7 25 absorbed absorb VERB admet-9 7 26     SPACE admet-9 7 27 fraction fraction NOUN admet-9 7 28     SPACE admet-9 7 29 or or CCONJ admet-9 7 30     SPACE admet-9 7 31 bioavailability bioavailability NOUN admet-9 7 32 ) ) PUNCT admet-9 7 33     SPACE admet-9 7 34 distribution distribution NOUN admet-9 7 35     SPACE admet-9 7 36 ( ( PUNCT admet-9 7 37 where where SCONJ admet-9 7 38     SPACE admet-9 7 39 the the DET admet-9 7 40     SPACE admet-9 7 41 drug drug NOUN admet-9 7 42     SPACE admet-9 7 43 is be AUX admet-9 7 44     SPACE admet-9 7 45 distributed distribute VERB admet-9 7 46 , , PUNCT admet-9 7 47     SPACE admet-9 7 48 how how SCONJ admet-9 7 49     SPACE admet-9 7 50 fast fast VERB admet-9 7 51     SPACE admet-9 7 52 and and CCONJ admet-9 7 53     SPACE admet-9 7 54 how how SCONJ admet-9 7 55     SPACE admet-9 7 56 extensive extensive ADJ admet-9 7 57 ) ) PUNCT admet-9 7 58     SPACE admet-9 7 59 metabolism metabolism NOUN admet-9 7 60     SPACE admet-9 7 61 ( ( PUNCT admet-9 7 62 how how SCONJ admet-9 7 63     SPACE admet-9 7 64 fast fast VERB admet-9 7 65 , , PUNCT admet-9 7 66     SPACE admet-9 7 67 what what PRON admet-9 7 68     SPACE admet-9 7 69 mechanism mechanism NOUN admet-9 7 70 / / SYM admet-9 7 71 route route NOUN admet-9 7 72 , , PUNCT admet-9 7 73     SPACE admet-9 7 74 what what PRON admet-9 7 75     SPACE admet-9 7 76 metabolite metabolite NOUN admet-9 7 77     SPACE admet-9 7 78 is be AUX admet-9 7 79     SPACE admet-9 7 80 formed form VERB admet-9 7 81 , , PUNCT admet-9 7 82     SPACE admet-9 7 83 and and CCONJ admet-9 7 84     SPACE admet-9 7 85 whether whether SCONJ admet-9 7 86     SPACE admet-9 7 87 they they PRON admet-9 7 88     SPACE admet-9 7 89 are be AUX admet-9 7 90     SPACE admet-9 7 91 active active ADJ admet-9 7 92     SPACE admet-9 7 93 or or CCONJ admet-9 7 94     SPACE admet-9 7 95 toxic toxic ADJ admet-9 7 96 ) ) PUNCT admet-9 7 97     SPACE admet-9 7 98 elimination elimination NOUN admet-9 7 99     SPACE admet-9 7 100 ( ( PUNCT admet-9 7 101 how how SCONJ admet-9 7 102     SPACE admet-9 7 103 fast fast VERB admet-9 7 104 , , PUNCT admet-9 7 105     SPACE admet-9 7 106 which which DET admet-9 7 107     SPACE admet-9 7 108 route route NOUN admet-9 7 109 ) ) PUNCT admet-9 7 110 . . PUNCT admet-9 7 111     SPACE admet-9 8 1 in in ADP admet-9 8 2     SPACE admet-9 8 3 the the DET admet-9 8 4     SPACE admet-9 8 5 drug drug NOUN admet-9 8 6     SPACE admet-9 8 7 discovery discovery NOUN admet-9 8 8     SPACE admet-9 8 9 process process NOUN admet-9 8 10 , , PUNCT admet-9 8 11     SPACE admet-9 8 12 early early ADV admet-9 8 13     SPACE admet-9 8 14 in in ADP admet-9 8 15     SPACE admet-9 8 16 vitro vitro VERB admet-9 8 17     SPACE admet-9 8 18 adme adme NOUN admet-9 8 19     SPACE admet-9 8 20 screening screening NOUN admet-9 8 21     SPACE admet-9 8 22 and and CCONJ admet-9 8 23     SPACE admet-9 8 24 in in ADP admet-9 8 25     SPACE admet-9 8 26 vivo vivo NOUN admet-9 8 27     SPACE admet-9 8 28 pk pk NOUN admet-9 8 29     SPACE admet-9 8 30 profiling profiling NOUN admet-9 8 31     SPACE admet-9 8 32 provide provide VERB admet-9 8 33     SPACE admet-9 8 34 a a DET admet-9 8 35     SPACE admet-9 8 36 basis basis NOUN admet-9 8 37     SPACE admet-9 8 38 for for ADP admet-9 8 39     SPACE admet-9 8 40 choosing choose VERB admet-9 8 41     SPACE admet-9 8 42 new new ADJ admet-9 8 43     SPACE admet-9 8 44 molecular molecular ADJ admet-9 8 45     SPACE admet-9 8 46 entities entity NOUN admet-9 8 47     SPACE admet-9 8 48 ( ( PUNCT admet-9 8 49 nmes nme NOUN admet-9 8 50 ) ) PUNCT admet-9 8 51     SPACE admet-9 8 52 and and CCONJ admet-9 8 53     SPACE admet-9 8 54 lead lead NOUN admet-9 8 55     SPACE admet-9 8 56 compounds compound VERB admet-9 8 57     SPACE admet-9 8 58 that that PRON admet-9 8 59     SPACE admet-9 8 60 have have VERB admet-9 8 61     SPACE admet-9 8 62 desirable desirable ADJ admet-9 8 63     SPACE admet-9 8 64 drug drug NOUN admet-9 8 65     SPACE admet-9 8 66 metabolism metabolism NOUN admet-9 8 67 , , PUNCT admet-9 8 68     SPACE admet-9 8 69 pk pk NOUN admet-9 8 70     SPACE admet-9 8 71 or or CCONJ admet-9 8 72     SPACE admet-9 8 73 safety safety NOUN admet-9 8 74     SPACE admet-9 8 75 profiles profile NOUN admet-9 8 76 , , PUNCT admet-9 8 77     SPACE admet-9 8 78 necessary necessary ADJ admet-9 8 79     SPACE admet-9 8 80 for for ADP admet-9 8 81     SPACE admet-9 8 82 drug drug NOUN admet-9 8 83     SPACE admet-9 8 84 candidate candidate NOUN admet-9 8 85     SPACE admet-9 8 86 selection selection NOUN admet-9 8 87     SPACE admet-9 8 88 ( ( PUNCT admet-9 8 89 cs cs PROPN admet-9 8 90 ) ) PUNCT admet-9 8 91     SPACE admet-9 8 92 and and CCONJ admet-9 8 93     SPACE admet-9 8 94 late‐stage late‐stage NOUN admet-9 8 95     SPACE admet-9 8 96 preclinical preclinical NOUN admet-9 8 97     SPACE admet-9 8 98 and and CCONJ admet-9 8 99     SPACE admet-9 8 100 clinical clinical ADJ admet-9 8 101     SPACE admet-9 8 102 development development NOUN admet-9 8 103 . . PUNCT admet-9 8 104     SPACE admet-9 9 1 the the DET admet-9 9 2     SPACE admet-9 9 3 adme adme NOUN admet-9 9 4     SPACE admet-9 9 5 properties property NOUN admet-9 9 6     SPACE admet-9 9 7 of of ADP admet-9 9 8     SPACE admet-9 9 9 a a DET admet-9 9 10     SPACE admet-9 9 11 drug drug NOUN admet-9 9 12     SPACE admet-9 9 13 allow allow VERB admet-9 9 14     SPACE admet-9 9 15 the the DET admet-9 9 16     SPACE admet-9 9 17 drug drug NOUN admet-9 9 18     SPACE admet-9 9 19 developer developer NOUN admet-9 9 20     SPACE admet-9 9 21 to to PART admet-9 9 22     SPACE admet-9 9 23 understand understand VERB admet-9 9 24     SPACE admet-9 9 25 the the DET admet-9 9 26     SPACE admet-9 9 27 safety safety NOUN admet-9 9 28     SPACE admet-9 9 29 and and CCONJ admet-9 9 30     SPACE admet-9 9 31 efficacy efficacy NOUN admet-9 9 32     SPACE admet-9 9 33 data datum NOUN admet-9 9 34     SPACE admet-9 9 35 required require VERB admet-9 9 36     SPACE admet-9 9 37 for for ADP admet-9 9 38     SPACE admet-9 9 39 regulatory regulatory ADJ admet-9 9 40     SPACE admet-9 9 41 approval approval NOUN admet-9 9 42 . . PUNCT admet-9 9 43         SPACE admet-9 10 1 wan wan PROPN admet-9 10 2         SPACE admet-9 10 3 admet admet X admet-9 10 4     SPACE admet-9 10 5 & & CCONJ admet-9 10 6     SPACE admet-9 10 7 dmpk dmpk VERB admet-9 10 8     SPACE admet-9 10 9 1(3 1(3 NUM admet-9 10 10 ) ) PUNCT admet-9 10 11     SPACE admet-9 10 12 ( ( PUNCT admet-9 10 13 2013 2013 NUM admet-9 10 14 ) ) PUNCT admet-9 10 15     SPACE admet-9 10 16 19‐28 19‐28 NUM admet-9 10 17     SPACE admet-9 10 18 20 20 NUM admet-9 10 19         SPACE admet-9 10 20 today today NOUN admet-9 10 21 , , PUNCT admet-9 10 22     SPACE admet-9 10 23 dmpk dmpk NOUN admet-9 10 24     SPACE admet-9 10 25 studies study NOUN admet-9 10 26     SPACE admet-9 10 27 performed perform VERB admet-9 10 28     SPACE admet-9 10 29 in in ADP admet-9 10 30     SPACE admet-9 10 31 vitro vitro VERB admet-9 10 32     SPACE admet-9 10 33 and and CCONJ admet-9 10 34     SPACE admet-9 10 35 in in ADP admet-9 10 36     SPACE admet-9 10 37 vivo vivo NOUN admet-9 10 38     SPACE admet-9 10 39 have have AUX admet-9 10 40     SPACE admet-9 10 41 become become VERB admet-9 10 42     SPACE admet-9 10 43 more more ADV admet-9 10 44     SPACE admet-9 10 45 standardised standardised ADJ admet-9 10 46     SPACE admet-9 10 47 procedures procedure NOUN admet-9 10 48     SPACE admet-9 10 49 across across ADP admet-9 10 50     SPACE admet-9 10 51 the the DET admet-9 10 52     SPACE admet-9 10 53 pharmaceutical pharmaceutical NOUN admet-9 10 54     SPACE admet-9 10 55 industry industry NOUN admet-9 10 56 . . PUNCT admet-9 10 57     SPACE admet-9 11 1 a a DET admet-9 11 2     SPACE admet-9 11 3 couple couple NOUN admet-9 11 4     SPACE admet-9 11 5 of of ADP admet-9 11 6     SPACE admet-9 11 7 typical typical ADJ admet-9 11 8     SPACE admet-9 11 9 examples example NOUN admet-9 11 10     SPACE admet-9 11 11 include include VERB admet-9 11 12     SPACE admet-9 11 13 the the PRON admet-9 11 14     SPACE admet-9 11 15 most most ADV admet-9 11 16     SPACE admet-9 11 17 commonly commonly ADV admet-9 11 18     SPACE admet-9 11 19 used use VERB admet-9 11 20     SPACE admet-9 11 21 in in ADP admet-9 11 22     SPACE admet-9 11 23 vitro vitro VERB admet-9 11 24     SPACE admet-9 11 25 adme adme NOUN admet-9 11 26     SPACE admet-9 11 27 studies study NOUN admet-9 11 28 , , PUNCT admet-9 11 29     SPACE admet-9 11 30 such such ADJ admet-9 11 31     SPACE admet-9 11 32 as as ADP admet-9 11 33     SPACE admet-9 11 34 liver liver NOUN admet-9 11 35     SPACE admet-9 11 36 microsomes microsome NOUN admet-9 11 37     SPACE admet-9 11 38 and and CCONJ admet-9 11 39     SPACE admet-9 11 40 the the DET admet-9 11 41     SPACE admet-9 11 42 whole whole ADJ admet-9 11 43     SPACE admet-9 11 44 hepatocyte hepatocyte NOUN admet-9 11 45     SPACE admet-9 11 46 models model NOUN admet-9 11 47     SPACE admet-9 11 48 for for ADP admet-9 11 49     SPACE admet-9 11 50 in in ADP admet-9 11 51     SPACE admet-9 11 52 vitro vitro VERB admet-9 11 53     SPACE admet-9 11 54 metabolism metabolism NOUN admet-9 11 55 . . PUNCT admet-9 11 56     SPACE admet-9 12 1 both both DET admet-9 12 2     SPACE admet-9 12 3 models model NOUN admet-9 12 4     SPACE admet-9 12 5 contain contain VERB admet-9 12 6     SPACE admet-9 12 7 major major ADJ admet-9 12 8     SPACE admet-9 12 9 metabolism metabolism NOUN admet-9 12 10     SPACE admet-9 12 11 enzymes enzyme NOUN admet-9 12 12 , , PUNCT admet-9 12 13     SPACE admet-9 12 14 such such ADJ admet-9 12 15     SPACE admet-9 12 16 as as ADP admet-9 12 17     SPACE admet-9 12 18 cyp450 cyp450 NOUN admet-9 12 19     SPACE admet-9 12 20 for for ADP admet-9 12 21     SPACE admet-9 12 22 phase phase NOUN admet-9 12 23     SPACE admet-9 12 24 i i PRON admet-9 12 25     SPACE admet-9 12 26 metabolism metabolism NOUN admet-9 12 27     SPACE admet-9 12 28 and and CCONJ admet-9 12 29     SPACE admet-9 12 30 udp‐glucuronosyltransferase udp‐glucuronosyltransferase VERB admet-9 12 31     SPACE admet-9 12 32 ( ( PUNCT admet-9 12 33 ugt ugt PROPN admet-9 12 34 ) ) PUNCT admet-9 12 35     SPACE admet-9 12 36 for for ADP admet-9 12 37     SPACE admet-9 12 38 phase phase NOUN admet-9 12 39     SPACE admet-9 12 40 ii ii NOUN admet-9 12 41     SPACE admet-9 12 42 metabolism metabolism NOUN admet-9 12 43 . . PUNCT admet-9 12 44     SPACE admet-9 13 1 these these DET admet-9 13 2     SPACE admet-9 13 3 relevant relevant ADJ admet-9 13 4     SPACE admet-9 13 5 in in ADP admet-9 13 6     SPACE admet-9 13 7 vitro vitro VERB admet-9 13 8     SPACE admet-9 13 9 models model NOUN admet-9 13 10     SPACE admet-9 13 11 are be AUX admet-9 13 12     SPACE admet-9 13 13 also also ADV admet-9 13 14     SPACE admet-9 13 15 applied apply VERB admet-9 13 16     SPACE admet-9 13 17 to to ADP admet-9 13 18     SPACE admet-9 13 19 cyp cyp ADJ admet-9 13 20     SPACE admet-9 13 21 inhibition inhibition NOUN admet-9 13 22 / / SYM admet-9 13 23 induction induction NOUN admet-9 13 24     SPACE admet-9 13 25 studies study NOUN admet-9 13 26     SPACE admet-9 13 27 as as ADV admet-9 13 28     SPACE admet-9 13 29 well well ADV admet-9 13 30     SPACE admet-9 13 31 as as ADP admet-9 13 32     SPACE admet-9 13 33 drug drug NOUN admet-9 13 34     SPACE admet-9 13 35 metabolite metabolite NOUN admet-9 13 36     SPACE admet-9 13 37 identification identification NOUN admet-9 13 38     SPACE admet-9 13 39 and and CCONJ admet-9 13 40     SPACE admet-9 13 41 profiling profiling NOUN admet-9 13 42     SPACE admet-9 13 43 across across ADP admet-9 13 44     SPACE admet-9 13 45 species specie NOUN admet-9 13 46 . . PUNCT admet-9 13 47     SPACE admet-9 14 1 other other ADJ admet-9 14 2     SPACE admet-9 14 3 key key NOUN admet-9 14 4     SPACE admet-9 14 5 in in ADP admet-9 14 6     SPACE admet-9 14 7 vitro vitro VERB admet-9 14 8     SPACE admet-9 14 9 assays assay NOUN admet-9 14 10 , , PUNCT admet-9 14 11     SPACE admet-9 14 12 such such ADJ admet-9 14 13     SPACE admet-9 14 14 as as ADP admet-9 14 15     SPACE admet-9 14 16 caco‐2 caco‐2 PROPN admet-9 14 17     SPACE admet-9 14 18 or or CCONJ admet-9 14 19     SPACE admet-9 14 20 mdck mdck ADV admet-9 14 21     SPACE admet-9 14 22 cell‐based cell‐based ADJ admet-9 14 23     SPACE admet-9 14 24 models model NOUN admet-9 14 25     SPACE admet-9 14 26 are be AUX admet-9 14 27     SPACE admet-9 14 28 often often ADV admet-9 14 29     SPACE admet-9 14 30 used use VERB admet-9 14 31     SPACE admet-9 14 32 for for ADP admet-9 14 33     SPACE admet-9 14 34 intestinal intestinal ADJ admet-9 14 35     SPACE admet-9 14 36 permeability permeability NOUN admet-9 14 37     SPACE admet-9 14 38 evaluation evaluation NOUN admet-9 14 39 . . PUNCT admet-9 14 40     SPACE admet-9 15 1 for for ADP admet-9 15 2     SPACE admet-9 15 3 in in ADP admet-9 15 4     SPACE admet-9 15 5 vivo vivo NOUN admet-9 15 6     SPACE admet-9 15 7 pk pk NOUN admet-9 15 8     SPACE admet-9 15 9 studies study NOUN admet-9 15 10 , , PUNCT admet-9 15 11     SPACE admet-9 15 12 association association NOUN admet-9 15 13     SPACE admet-9 15 14 for for ADP admet-9 15 15     SPACE admet-9 15 16 assessment assessment NOUN admet-9 15 17     SPACE admet-9 15 18 and and CCONJ admet-9 15 19     SPACE admet-9 15 20 accreditation accreditation NOUN admet-9 15 21     SPACE admet-9 15 22 of of ADP admet-9 15 23     SPACE admet-9 15 24 laboratory laboratory NOUN admet-9 15 25     SPACE admet-9 15 26 animal animal NOUN admet-9 15 27     SPACE admet-9 15 28 care care NOUN admet-9 15 29     SPACE admet-9 15 30 ( ( PUNCT admet-9 15 31 aaalac)‐accredited aaalac)‐accredite VERB admet-9 15 32     SPACE admet-9 15 33 animals animal NOUN admet-9 15 34 , , PUNCT admet-9 15 35     SPACE admet-9 15 36 such such ADJ admet-9 15 37     SPACE admet-9 15 38 as as ADP admet-9 15 39     SPACE admet-9 15 40 mice mouse NOUN admet-9 15 41 , , PUNCT admet-9 15 42     SPACE admet-9 15 43 rats rat NOUN admet-9 15 44 , , PUNCT admet-9 15 45     SPACE admet-9 15 46 dogs dog NOUN admet-9 15 47 , , PUNCT admet-9 15 48     SPACE admet-9 15 49 and and CCONJ admet-9 15 50     SPACE admet-9 15 51 non‐human non‐human NOUN admet-9 15 52     SPACE admet-9 15 53 primates primate NOUN admet-9 15 54     SPACE admet-9 15 55 are be AUX admet-9 15 56     SPACE admet-9 15 57 employed employ VERB admet-9 15 58     SPACE admet-9 15 59 to to PART admet-9 15 60     SPACE admet-9 15 61 generate generate VERB admet-9 15 62     SPACE admet-9 15 63 in in ADP admet-9 15 64     SPACE admet-9 15 65 vivo vivo NOUN admet-9 15 66     SPACE admet-9 15 67 pk pk NOUN admet-9 15 68     SPACE admet-9 15 69 data datum NOUN admet-9 15 70     SPACE admet-9 15 71 like like ADP admet-9 15 72     SPACE admet-9 15 73 drug drug NOUN admet-9 15 74     SPACE admet-9 15 75 clearance clearance NOUN admet-9 15 76     SPACE admet-9 15 77 ( ( PUNCT admet-9 15 78 cl cl NOUN admet-9 15 79 ) ) PUNCT admet-9 15 80 , , PUNCT admet-9 15 81     SPACE admet-9 15 82 bioavailability bioavailability NOUN admet-9 15 83     SPACE admet-9 15 84 ( ( PUNCT admet-9 15 85 f% f% NOUN admet-9 15 86 ) ) PUNCT admet-9 15 87 , , PUNCT admet-9 15 88     SPACE admet-9 15 89 exposure exposure NOUN admet-9 15 90     SPACE admet-9 15 91 ( ( PUNCT admet-9 15 92 auc auc NOUN admet-9 15 93 ) ) PUNCT admet-9 15 94 , , PUNCT admet-9 15 95     SPACE admet-9 15 96 half half ADJ admet-9 15 97     SPACE admet-9 15 98 life life NOUN admet-9 15 99     SPACE admet-9 15 100 ( ( PUNCT admet-9 15 101 t1/2 t1/2 PROPN admet-9 15 102 ) ) PUNCT admet-9 15 103 , , PUNCT admet-9 15 104     SPACE admet-9 15 105 and and CCONJ admet-9 15 106     SPACE admet-9 15 107 distribution distribution NOUN admet-9 15 108     SPACE admet-9 15 109 volume volume NOUN admet-9 15 110     SPACE admet-9 15 111 ( ( PUNCT admet-9 15 112 l l NOUN admet-9 15 113 ) ) PUNCT admet-9 15 114 . . PUNCT admet-9 15 115     SPACE admet-9 16 1 currently currently ADV admet-9 16 2 , , PUNCT admet-9 16 3     SPACE admet-9 16 4 almost almost ADV admet-9 16 5     SPACE admet-9 16 6 all all PRON admet-9 16 7     SPACE admet-9 16 8 dmpk‐related dmpk‐relate VERB admet-9 16 9     SPACE admet-9 16 10 assays assay NOUN admet-9 16 11     SPACE admet-9 16 12 are be AUX admet-9 16 13     SPACE admet-9 16 14 carried carry VERB admet-9 16 15     SPACE admet-9 16 16 out out ADP admet-9 16 17     SPACE admet-9 16 18 by by ADP admet-9 16 19     SPACE admet-9 16 20 available available ADJ admet-9 16 21     SPACE admet-9 16 22 automated automate VERB admet-9 16 23     SPACE admet-9 16 24 technology technology NOUN admet-9 16 25     SPACE admet-9 16 26 platforms platform NOUN admet-9 16 27     SPACE admet-9 16 28 combined combine VERB admet-9 16 29     SPACE admet-9 16 30 with with ADP admet-9 16 31     SPACE admet-9 16 32 high‐throughput high‐throughput ADJ admet-9 16 33     SPACE admet-9 16 34 liquid liquid NOUN admet-9 16 35     SPACE admet-9 16 36 chromatography‐mass chromatography‐mass NOUN admet-9 16 37     SPACE admet-9 16 38 spectrometry spectrometry NOUN admet-9 16 39     SPACE admet-9 16 40 ( ( PUNCT admet-9 16 41 lc lc PROPN admet-9 16 42 / / SYM admet-9 16 43 ms ms PROPN admet-9 16 44 / / SYM admet-9 16 45 ms ms NOUN admet-9 16 46 ) ) PUNCT admet-9 16 47     SPACE admet-9 16 48 bioanalysis bioanalysis NOUN admet-9 16 49 , , PUNCT admet-9 16 50     SPACE admet-9 16 51 which which PRON admet-9 16 52     SPACE admet-9 16 53 has have AUX admet-9 16 54     SPACE admet-9 16 55 considerably considerably ADV admet-9 16 56     SPACE admet-9 16 57 speeded speed VERB admet-9 16 58     SPACE admet-9 16 59 up up ADP admet-9 16 60     SPACE admet-9 16 61 the the DET admet-9 16 62     SPACE admet-9 16 63 adme adme NOUN admet-9 16 64     SPACE admet-9 16 65 data data NOUN admet-9 16 66     SPACE admet-9 16 67 generation generation NOUN admet-9 16 68     SPACE admet-9 16 69 for for ADP admet-9 16 70     SPACE admet-9 16 71 decision‐making decision‐making NOUN admet-9 16 72     SPACE admet-9 16 73 during during ADP admet-9 16 74     SPACE admet-9 16 75 the the DET admet-9 16 76     SPACE admet-9 16 77 drug drug NOUN admet-9 16 78     SPACE admet-9 16 79 discovery discovery NOUN admet-9 16 80     SPACE admet-9 16 81 and and CCONJ admet-9 16 82     SPACE admet-9 16 83 development development NOUN admet-9 16 84     SPACE admet-9 16 85 process process NOUN admet-9 16 86 . . PUNCT admet-9 16 87         SPACE admet-9 17 1 2 2 NUM admet-9 17 2 . . PUNCT admet-9 17 3     SPACE admet-9 17 4 what what PRON admet-9 17 5     SPACE admet-9 17 6 adme adme NOUN admet-9 17 7     SPACE admet-9 17 8 tests test NOUN admet-9 17 9     SPACE admet-9 17 10 should should AUX admet-9 17 11     SPACE admet-9 17 12 be be AUX admet-9 17 13     SPACE admet-9 17 14 conducted conduct VERB admet-9 17 15     SPACE admet-9 17 16 for for ADP admet-9 17 17     SPACE admet-9 17 18 preclinical preclinical ADJ admet-9 17 19     SPACE admet-9 17 20 studies study NOUN admet-9 17 21 ? ? PUNCT admet-9 17 22             SPACE admet-9 17 23 potency potency NOUN admet-9 17 24 < < X admet-9 17 25 100 100 NUM admet-9 17 26 nm nm ADJ admet-9 17 27 enzyme enzyme NOUN admet-9 17 28 / / SYM admet-9 17 29 cell cell NOUN admet-9 17 30 based base VERB admet-9 17 31 assays assay NOUN admet-9 17 32 solubility solubility NOUN admet-9 17 33 7.4 7.4 NUM admet-9 17 34 > > SYM admet-9 17 35 1 1 NUM admet-9 17 36 - - SYM admet-9 17 37 10 10 NUM admet-9 17 38 µm µm NOUN admet-9 17 39 ( ( PUNCT admet-9 17 40 pbs pbs PROPN admet-9 17 41 buffer buffer NOUN admet-9 17 42 ) ) PUNCT admet-9 17 43 metabolic metabolic NOUN admet-9 17 44 stability stability NOUN admet-9 17 45 clint clint NOUN admet-9 17 46 ( ( PUNCT admet-9 17 47 h h NOUN admet-9 17 48 , , PUNCT admet-9 17 49 r r NOUN admet-9 17 50 , , PUNCT admet-9 17 51 d d PROPN admet-9 17 52 , , PUNCT admet-9 17 53 m m NOUN admet-9 17 54 ) ) PUNCT admet-9 17 55 caco-2 caco-2 NUM admet-9 17 56 permeability permeability NOUN admet-9 17 57 > > X admet-9 17 58 0.3x 0.3x NOUN admet-9 17 59 1e-6cm 1e-6cm NUM admet-9 17 60 / / SYM admet-9 17 61 s s PROPN admet-9 17 62 , , PUNCT admet-9 17 63 efflux efflux VERB admet-9 17 64 logd7.4 logd7.4 PUNCT admet-9 17 65 ( ( PUNCT admet-9 17 66 1.5 1.5 NUM admet-9 17 67 - - SYM admet-9 17 68 4.5 4.5 NUM admet-9 17 69 ) ) PUNCT admet-9 17 70 in in ADP admet-9 17 71 vivo vivo ADJ admet-9 17 72 pk pk NOUN admet-9 17 73 ( ( PUNCT admet-9 17 74 m m PROPN admet-9 17 75 , , PUNCT admet-9 17 76 r r NOUN admet-9 17 77 , , PUNCT admet-9 17 78 d d PROPN admet-9 17 79 , , PUNCT admet-9 17 80 m m NOUN admet-9 17 81 ) ) PUNCT admet-9 17 82 f>20 f>20 SYM admet-9 17 83 % % NOUN admet-9 17 84 , , PUNCT admet-9 17 85 cl<50 cl<50 NOUN admet-9 17 86 % % NOUN admet-9 17 87 bf bf NOUN admet-9 17 88 , , PUNCT admet-9 17 89 dose<100 dose<100 NUM admet-9 17 90 mg mg PROPN admet-9 17 91 ppb ppb NOUN admet-9 17 92 ( ( PUNCT admet-9 17 93 r r NOUN admet-9 17 94 , , PUNCT admet-9 17 95 h h NOUN admet-9 17 96 , , PUNCT admet-9 17 97 d d PROPN admet-9 17 98 , , PUNCT admet-9 17 99 m m NOUN admet-9 17 100 ) ) PUNCT admet-9 17 101 fu fu NOUN admet-9 17 102 > > X admet-9 17 103 0.1 0.1 NUM admet-9 17 104 - - SYM admet-9 17 105 1 1 NUM admet-9 17 106 % % NOUN admet-9 17 107 cyp cyp ADJ admet-9 17 108 inhibition inhibition NOUN admet-9 17 109 ( ( PUNCT admet-9 17 110 ic50 ic50 PROPN admet-9 17 111 ) ) PUNCT admet-9 17 112 major major ADJ admet-9 17 113 cyp>1 cyp>1 PROPN admet-9 17 114 - - PUNCT admet-9 17 115 10 10 NUM admet-9 17 116 µm µm ADP admet-9 17 117 reactive reactive ADJ admet-9 17 118 metabolite metabolite NOUN admet-9 17 119 ( ( PUNCT admet-9 17 120 gsh gsh PROPN admet-9 17 121 ) ) PUNCT admet-9 17 122 met meet VERB admet-9 17 123 i i PROPN admet-9 17 124 d d PROPN admet-9 17 125 , , PUNCT admet-9 17 126 cyp cyp ADJ admet-9 17 127 i i PROPN admet-9 17 128 d d PROPN admet-9 17 129 metabolism metabolism NOUN admet-9 17 130 route route NOUN admet-9 17 131 pk pk PROPN admet-9 17 132 / / SYM admet-9 17 133 pd pd NOUN admet-9 17 134 dose dose NOUN admet-9 17 135 response response NOUN admet-9 17 136 solubility solubility NOUN admet-9 17 137 6.5 6.5 NUM admet-9 17 138 > > SYM admet-9 17 139 10 10 NUM admet-9 17 140 µm µm NOUN admet-9 17 141 ( ( PUNCT admet-9 17 142 fassif fassif NOUN admet-9 17 143 ) ) PUNCT admet-9 17 144 hepatocytes hepatocyte NOUN admet-9 17 145 ( ( PUNCT admet-9 17 146 r r NOUN admet-9 17 147 , , PUNCT admet-9 17 148 h h NOUN admet-9 17 149 ) ) PUNCT admet-9 17 150 blood blood NOUN admet-9 17 151 / / SYM admet-9 17 152 plasma plasma NOUN admet-9 17 153 ratio ratio NOUN admet-9 17 154 ( ( PUNCT admet-9 17 155 r r NOUN admet-9 17 156 , , PUNCT admet-9 17 157 h h NOUN admet-9 17 158 , , PUNCT admet-9 17 159 d d PROPN admet-9 17 160 , , PUNCT admet-9 17 161 m m NOUN admet-9 17 162 ) ) PUNCT admet-9 17 163 non non ADJ admet-9 17 164 - - ADJ admet-9 17 165 glp glp ADJ admet-9 17 166 tox tox NOUN admet-9 17 167 ( ( PUNCT admet-9 17 168 rodent rodent ADJ admet-9 17 169 , , PUNCT admet-9 17 170 dog dog NOUN admet-9 17 171 ) ) PUNCT admet-9 17 172 glp glp NOUN admet-9 17 173 tox tox PROPN admet-9 17 174 ( ( PUNCT admet-9 17 175 safety safety NOUN admet-9 17 176 package package NOUN admet-9 17 177 ) ) PUNCT admet-9 18 1 cs cs PROPN admet-9 18 2 ( ( PUNCT admet-9 18 3 candidate candidate NOUN admet-9 18 4 selection selection NOUN admet-9 18 5 ) ) PUNCT admet-9 18 6 cyp cyp ADJ admet-9 18 7 induction induction NOUN admet-9 18 8 h h NOUN admet-9 18 9 it it PRON admet-9 18 10 - - PUNCT admet-9 18 11 to to ADP admet-9 18 12 - - PUNCT admet-9 18 13 lead lead VERB admet-9 18 14 lead lead NOUN admet-9 18 15 - - PUNCT admet-9 18 16 optim optim ADJ admet-9 18 17 isation isation NOUN admet-9 18 18 c c PROPN admet-9 18 19 andidate andidate PROPN admet-9 18 20 transporter transporter NOUN admet-9 18 21 , , PUNCT admet-9 18 22 p p NOUN admet-9 18 23 - - PUNCT admet-9 18 24 gp gp NOUN admet-9 18 25 etc etc X admet-9 18 26 substrate substrate NOUN admet-9 18 27 / / SYM admet-9 18 28 inhibition inhibition NOUN admet-9 18 29 mdck mdck PROPN admet-9 18 30 pamap pamap NOUN admet-9 19 1 herg herg PROPN admet-9 20 1 ic50 ic50 PROPN admet-9 20 2 ind ind NOUN admet-9 20 3 enabling enable VERB admet-9 20 4 ( ( PUNCT admet-9 20 5 candidate candidate NOUN admet-9 20 6 ) ) PUNCT admet-9 20 7 clinical clinical ADJ admet-9 20 8 candidate candidate NOUN admet-9 20 9 ( ( PUNCT admet-9 20 10 glp glp PROPN admet-9 20 11 ) ) PUNCT admet-9 20 12 mtd mtd PROPN admet-9 20 13 ( ( PUNCT admet-9 20 14 rodent rodent NOUN admet-9 20 15 ) ) PUNCT admet-9 20 16 human human PROPN admet-9 20 17 pk pk NOUN admet-9 20 18 dose dose PROPN admet-9 20 19 , , PUNCT admet-9 20 20 pk pk PROPN admet-9 20 21 / / SYM admet-9 20 22 pd pd PROPN admet-9 20 23 f f PROPN admet-9 21 1 clce(ss)dose clce(ss)dose PROPN admet-9 21 2 τ•• τ•• PROPN admet-9 21 3 = = PUNCT admet-9 21 4     SPACE admet-9 21 5 figure figure NOUN admet-9 21 6     SPACE admet-9 21 7 1 1 NUM admet-9 21 8 : : PUNCT admet-9 21 9     SPACE admet-9 21 10 typical typical ADJ admet-9 21 11     SPACE admet-9 21 12 adme adme PROPN admet-9 21 13 / / SYM admet-9 21 14 pk pk NOUN admet-9 21 15     SPACE admet-9 21 16 screening screening NOUN admet-9 21 17     SPACE admet-9 21 18 cascade cascade NOUN admet-9 21 19         SPACE admet-9 21 20 figure figure NOUN admet-9 21 21     SPACE admet-9 21 22 1 1 NUM admet-9 21 23     SPACE admet-9 21 24 highlights highlight NOUN admet-9 21 25     SPACE admet-9 21 26 a a DET admet-9 21 27     SPACE admet-9 21 28 typical typical ADJ admet-9 21 29     SPACE admet-9 21 30 adme adme PROPN admet-9 21 31 / / SYM admet-9 21 32 dmpk dmpk NOUN admet-9 21 33     SPACE admet-9 21 34 screening screening NOUN admet-9 21 35     SPACE admet-9 21 36 cascade cascade NOUN admet-9 21 37     SPACE admet-9 21 38 to to PART admet-9 21 39     SPACE admet-9 21 40 support support VERB admet-9 21 41     SPACE admet-9 21 42 drug drug NOUN admet-9 21 43     SPACE admet-9 21 44 discovery discovery NOUN admet-9 21 45     SPACE admet-9 21 46 programs program NOUN admet-9 21 47     SPACE admet-9 21 48 from from ADP admet-9 21 49     SPACE admet-9 21 50 early early ADJ admet-9 21 51     SPACE admet-9 21 52 hit‐to‐lead hit‐to‐lead ADV admet-9 21 53 , , PUNCT admet-9 21 54     SPACE admet-9 21 55 to to PART admet-9 21 56     SPACE admet-9 21 57 lead lead VERB admet-9 21 58     SPACE admet-9 21 59 optimisation optimisation NOUN admet-9 21 60     SPACE admet-9 21 61 and and CCONJ admet-9 21 62     SPACE admet-9 21 63 candidate candidate NOUN admet-9 21 64     SPACE admet-9 21 65 evaluations evaluation NOUN admet-9 21 66 . . PUNCT admet-9 21 67     SPACE admet-9 22 1 as as SCONJ admet-9 22 2     SPACE admet-9 22 3 depicted depict VERB admet-9 22 4     SPACE admet-9 22 5 in in ADP admet-9 22 6     SPACE admet-9 22 7 figure figure NOUN admet-9 22 8     SPACE admet-9 22 9 1 1 NUM admet-9 22 10 , , PUNCT admet-9 22 11     SPACE admet-9 22 12 a a DET admet-9 22 13     SPACE admet-9 22 14 number number NOUN admet-9 22 15     SPACE admet-9 22 16 of of ADP admet-9 22 17     SPACE admet-9 22 18 dmpk dmpk NOUN admet-9 22 19     SPACE admet-9 22 20 studies study NOUN admet-9 22 21     SPACE admet-9 22 22 are be AUX admet-9 22 23     SPACE admet-9 22 24 required require VERB admet-9 22 25     SPACE admet-9 22 26 before before ADP admet-9 22 27     SPACE admet-9 22 28 cs cs X admet-9 22 29 , , PUNCT admet-9 22 30     SPACE admet-9 22 31 followed follow VERB admet-9 22 32     SPACE admet-9 22 33 by by ADP admet-9 22 34     SPACE admet-9 22 35 non‐glp non‐glp NOUN admet-9 22 36     SPACE admet-9 22 37 and and CCONJ admet-9 22 38     SPACE admet-9 22 39 glp glp NOUN admet-9 22 40     SPACE admet-9 22 41 toxicology toxicology NOUN admet-9 22 42     SPACE admet-9 22 43 studies study NOUN admet-9 22 44     SPACE admet-9 22 45 for for ADP admet-9 22 46     SPACE admet-9 22 47 the the DET admet-9 22 48     SPACE admet-9 22 49 ind‐enabling ind‐enabling NOUN admet-9 22 50     SPACE admet-9 22 51 package package NOUN admet-9 22 52     SPACE admet-9 22 53 that that PRON admet-9 22 54     SPACE admet-9 22 55 is be AUX admet-9 22 56     SPACE admet-9 22 57 necessary necessary ADJ admet-9 22 58     SPACE admet-9 22 59 for for ADP admet-9 22 60     SPACE admet-9 22 61 clinical clinical ADJ admet-9 22 62     SPACE admet-9 22 63 candidate candidate NOUN admet-9 22 64     SPACE admet-9 22 65 development development NOUN admet-9 22 66 . . PUNCT admet-9 22 67     SPACE admet-9 23 1 various various ADJ admet-9 23 2     SPACE admet-9 23 3 studies study NOUN admet-9 23 4     SPACE admet-9 23 5 and and CCONJ admet-9 23 6     SPACE admet-9 23 7 assays assay NOUN admet-9 23 8     SPACE admet-9 23 9 should should AUX admet-9 23 10     SPACE admet-9 23 11 be be AUX admet-9 23 12     SPACE admet-9 23 13 conducted conduct VERB admet-9 23 14     SPACE admet-9 23 15 at at ADP admet-9 23 16     SPACE admet-9 23 17 different different ADJ admet-9 23 18     SPACE admet-9 23 19 stages stage NOUN admet-9 23 20     SPACE admet-9 23 21 to to PART admet-9 23 22     SPACE admet-9 23 23 address address VERB admet-9 23 24     SPACE admet-9 23 25 adme adme NOUN admet-9 23 26     SPACE admet-9 23 27 issues issue NOUN admet-9 23 28     SPACE admet-9 23 29 and and CCONJ admet-9 23 30     SPACE admet-9 23 31 meet meet VERB admet-9 23 32     SPACE admet-9 23 33 specific specific ADJ admet-9 23 34     SPACE admet-9 23 35 criteria criterion NOUN admet-9 23 36     SPACE admet-9 23 37 to to PART admet-9 23 38     SPACE admet-9 23 39 enable enable VERB admet-9 23 40     SPACE admet-9 23 41 the the DET admet-9 23 42     SPACE admet-9 23 43 project project NOUN admet-9 23 44     SPACE admet-9 23 45 to to PART admet-9 23 46     SPACE admet-9 23 47 admet admet VERB admet-9 23 48     SPACE admet-9 23 49 & & CCONJ admet-9 23 50     SPACE admet-9 23 51 dmpk dmpk VERB admet-9 23 52     SPACE admet-9 23 53 1(3 1(3 NUM admet-9 23 54 ) ) PUNCT admet-9 23 55     SPACE admet-9 23 56 ( ( PUNCT admet-9 23 57 2013 2013 NUM admet-9 23 58 ) ) PUNCT admet-9 23 59     SPACE admet-9 23 60 19‐28 19‐28 NUM admet-9 23 61     SPACE admet-9 23 62 adme adme NOUN admet-9 23 63     SPACE admet-9 23 64 tests test NOUN admet-9 23 65     SPACE admet-9 23 66 for for ADP admet-9 23 67     SPACE admet-9 23 68 preclinical preclinical ADJ admet-9 23 69     SPACE admet-9 23 70 studies study NOUN admet-9 23 71     SPACE admet-9 23 72 doi doi NOUN admet-9 23 73 : : PUNCT admet-9 23 74     SPACE admet-9 23 75 10.5599 10.5599 NUM admet-9 23 76 / / SYM admet-9 23 77 admet.1.3.9 admet.1.3.9 NOUN admet-9 23 78     SPACE admet-9 23 79 21 21 NUM admet-9 23 80     SPACE admet-9 23 81 move move NOUN admet-9 23 82     SPACE admet-9 23 83 forward forward ADV admet-9 23 84 . . PUNCT admet-9 23 85     SPACE admet-9 24 1 it it PRON admet-9 24 2     SPACE admet-9 24 3 should should AUX admet-9 24 4     SPACE admet-9 24 5 be be AUX admet-9 24 6     SPACE admet-9 24 7 noted note VERB admet-9 24 8     SPACE admet-9 24 9 that that SCONJ admet-9 24 10     SPACE admet-9 24 11 these these DET admet-9 24 12     SPACE admet-9 24 13 criteria criterion NOUN admet-9 24 14 , , PUNCT admet-9 24 15     SPACE admet-9 24 16 as as SCONJ admet-9 24 17     SPACE admet-9 24 18 exemplified exemplify VERB admet-9 24 19     SPACE admet-9 24 20 in in ADP admet-9 24 21     SPACE admet-9 24 22 this this DET admet-9 24 23     SPACE admet-9 24 24 cascade cascade NOUN admet-9 24 25 , , PUNCT admet-9 24 26     SPACE admet-9 24 27 are be AUX admet-9 24 28     SPACE admet-9 24 29 not not PART admet-9 24 30     SPACE admet-9 24 31 fixed fix VERB admet-9 24 32     SPACE admet-9 24 33 numbers number NOUN admet-9 24 34     SPACE admet-9 24 35 or or CCONJ admet-9 24 36     SPACE admet-9 24 37 filters filter NOUN admet-9 24 38 , , PUNCT admet-9 24 39     SPACE admet-9 24 40 and and CCONJ admet-9 24 41     SPACE admet-9 24 42 depend depend VERB admet-9 24 43     SPACE admet-9 24 44 on on ADP admet-9 24 45     SPACE admet-9 24 46 other other ADJ admet-9 24 47     SPACE admet-9 24 48 parameters parameter NOUN admet-9 24 49     SPACE admet-9 24 50 as as ADV admet-9 24 51     SPACE admet-9 24 52 well well ADV admet-9 24 53     SPACE admet-9 24 54 as as ADP admet-9 24 55     SPACE admet-9 24 56 the the DET admet-9 24 57     SPACE admet-9 24 58 specific specific ADJ admet-9 24 59     SPACE admet-9 24 60 therapeutic therapeutic ADJ admet-9 24 61     SPACE admet-9 24 62 targets target NOUN admet-9 24 63     SPACE admet-9 24 64 of of ADP admet-9 24 65     SPACE admet-9 24 66 different different ADJ admet-9 24 67     SPACE admet-9 24 68 drug drug NOUN admet-9 24 69     SPACE admet-9 24 70 discovery discovery NOUN admet-9 24 71     SPACE admet-9 24 72 programs program NOUN admet-9 24 73 . . PUNCT admet-9 24 74     SPACE admet-9 25 1 this this DET admet-9 25 2     SPACE admet-9 25 3 cascade cascade NOUN admet-9 25 4     SPACE admet-9 25 5 just just ADV admet-9 25 6     SPACE admet-9 25 7 demonstrates demonstrate VERB admet-9 25 8     SPACE admet-9 25 9 a a DET admet-9 25 10     SPACE admet-9 25 11 traditional traditional ADJ admet-9 25 12     SPACE admet-9 25 13 downstream downstream NOUN admet-9 25 14     SPACE admet-9 25 15 of of ADP admet-9 25 16     SPACE admet-9 25 17 adme adme NOUN admet-9 25 18 / / SYM admet-9 25 19 pk pk NOUN admet-9 25 20     SPACE admet-9 25 21 tests test NOUN admet-9 25 22     SPACE admet-9 25 23 for for ADP admet-9 25 24     SPACE admet-9 25 25 a a DET admet-9 25 26     SPACE admet-9 25 27 typical typical ADJ admet-9 25 28     SPACE admet-9 25 29 drug drug NOUN admet-9 25 30     SPACE admet-9 25 31 discovery discovery NOUN admet-9 25 32     SPACE admet-9 25 33 programs program NOUN admet-9 25 34     SPACE admet-9 25 35 before before ADP admet-9 25 36     SPACE admet-9 25 37 the the DET admet-9 25 38     SPACE admet-9 25 39 ind‐enabling ind‐enable VERB admet-9 25 40     SPACE admet-9 25 41 stage stage NOUN admet-9 25 42 . . PUNCT admet-9 25 43     SPACE admet-9 25 44 often often ADV admet-9 25 45 , , PUNCT admet-9 25 46     SPACE admet-9 25 47 at at ADP admet-9 25 48     SPACE admet-9 25 49 the the DET admet-9 25 50     SPACE admet-9 25 51 early early ADJ admet-9 25 52     SPACE admet-9 25 53 stage stage NOUN admet-9 25 54     SPACE admet-9 25 55 of of ADP admet-9 25 56     SPACE admet-9 25 57 hit‐to‐lead hit‐to‐lead PROPN admet-9 25 58 , , PUNCT admet-9 25 59     SPACE admet-9 25 60 key key NOUN admet-9 25 61     SPACE admet-9 25 62 in in ADP admet-9 25 63     SPACE admet-9 25 64 vitro vitro VERB admet-9 25 65     SPACE admet-9 25 66 assays assay NOUN admet-9 25 67     SPACE admet-9 25 68 and and CCONJ admet-9 25 69     SPACE admet-9 25 70 studies study NOUN admet-9 25 71 , , PUNCT admet-9 25 72     SPACE admet-9 25 73 such such ADJ admet-9 25 74     SPACE admet-9 25 75 as as ADP admet-9 25 76     SPACE admet-9 25 77 solubility solubility NOUN admet-9 25 78 , , PUNCT admet-9 25 79     SPACE admet-9 25 80 liver liver NOUN admet-9 25 81     SPACE admet-9 25 82 microsomal microsomal ADJ admet-9 25 83     SPACE admet-9 25 84 stability stability NOUN admet-9 25 85 , , PUNCT admet-9 25 86     SPACE admet-9 25 87 cyp cyp ADJ admet-9 25 88     SPACE admet-9 25 89 inhibition inhibition NOUN admet-9 25 90 , , PUNCT admet-9 25 91     SPACE admet-9 25 92 and and CCONJ admet-9 25 93     SPACE admet-9 25 94 permeability permeability NOUN admet-9 25 95     SPACE admet-9 25 96 should should AUX admet-9 25 97     SPACE admet-9 25 98 be be AUX admet-9 25 99     SPACE admet-9 25 100 conducted conduct VERB admet-9 25 101     SPACE admet-9 25 102 to to PART admet-9 25 103     SPACE admet-9 25 104 provide provide VERB admet-9 25 105     SPACE admet-9 25 106 key key ADJ admet-9 25 107     SPACE admet-9 25 108 data datum NOUN admet-9 25 109     SPACE admet-9 25 110 for for ADP admet-9 25 111     SPACE admet-9 25 112 chemists chemist NOUN admet-9 25 113     SPACE admet-9 25 114 to to PART admet-9 25 115     SPACE admet-9 25 116 select select VERB admet-9 25 117     SPACE admet-9 25 118 the the PRON admet-9 25 119     SPACE admet-9 25 120 more more ADJ admet-9 25 121     SPACE admet-9 25 122 metabolically metabolically NOUN admet-9 25 123     SPACE admet-9 25 124 stable stable ADJ admet-9 25 125     SPACE admet-9 25 126 and and CCONJ admet-9 25 127     SPACE admet-9 25 128 active active ADJ admet-9 25 129 / / SYM admet-9 25 130 potent potent NOUN admet-9 25 131     SPACE admet-9 25 132 compounds compound NOUN admet-9 25 133     SPACE admet-9 25 134 for for ADP admet-9 25 135     SPACE admet-9 25 136 further far ADV admet-9 25 137     SPACE admet-9 25 138 in in ADP admet-9 25 139     SPACE admet-9 25 140 vivo vivo NOUN admet-9 25 141     SPACE admet-9 25 142 pk pk NOUN admet-9 25 143     SPACE admet-9 25 144 studies study NOUN admet-9 25 145 . . PUNCT admet-9 25 146     SPACE admet-9 26 1 solubility solubility NOUN admet-9 26 2     SPACE admet-9 26 3 and and CCONJ admet-9 26 4     SPACE admet-9 26 5 log log NOUN admet-9 26 6     SPACE admet-9 26 7 d d NOUN admet-9 26 8     SPACE admet-9 26 9 data datum NOUN admet-9 26 10     SPACE admet-9 26 11 can can AUX admet-9 26 12     SPACE admet-9 26 13 serve serve VERB admet-9 26 14     SPACE admet-9 26 15 as as ADP admet-9 26 16     SPACE admet-9 26 17 a a DET admet-9 26 18     SPACE admet-9 26 19 basis basis NOUN admet-9 26 20     SPACE admet-9 26 21 to to PART admet-9 26 22     SPACE admet-9 26 23 run run VERB admet-9 26 24     SPACE admet-9 26 25 various various ADJ admet-9 26 26     SPACE admet-9 26 27 in in ADP admet-9 26 28     SPACE admet-9 26 29 vitro vitro VERB admet-9 26 30     SPACE admet-9 26 31 assays assay NOUN admet-9 26 32     SPACE admet-9 26 33 as as ADV admet-9 26 34     SPACE admet-9 26 35 well well ADV admet-9 26 36     SPACE admet-9 26 37 as as ADP admet-9 26 38     SPACE admet-9 26 39 for for ADP admet-9 26 40     SPACE admet-9 26 41 drug drug NOUN admet-9 26 42     SPACE admet-9 26 43 stability stability NOUN admet-9 26 44     SPACE admet-9 26 45 assessment assessment NOUN admet-9 26 46     SPACE admet-9 26 47 and and CCONJ admet-9 26 48     SPACE admet-9 26 49 selection selection NOUN admet-9 26 50     SPACE admet-9 26 51 of of ADP admet-9 26 52     SPACE admet-9 26 53 suitable suitable ADJ admet-9 26 54     SPACE admet-9 26 55 formulations formulation NOUN admet-9 26 56 . . PUNCT admet-9 26 57     SPACE admet-9 26 58 also also ADV admet-9 26 59 , , PUNCT admet-9 26 60     SPACE admet-9 26 61 it it PRON admet-9 26 62     SPACE admet-9 26 63 is be AUX admet-9 26 64     SPACE admet-9 26 65 well well ADV admet-9 26 66     SPACE admet-9 26 67 known know VERB admet-9 26 68     SPACE admet-9 26 69 that that PRON admet-9 26 70     SPACE admet-9 26 71 log log VERB admet-9 26 72     SPACE admet-9 26 73 d d PROPN admet-9 26 74 / / SYM admet-9 26 75 log log NOUN admet-9 26 76     SPACE admet-9 26 77 p p NOUN admet-9 26 78     SPACE admet-9 26 79 a a DET admet-9 26 80     SPACE admet-9 26 81 crucial crucial ADJ admet-9 26 82     SPACE admet-9 26 83 factor factor NOUN admet-9 26 84     SPACE admet-9 26 85 governing govern VERB admet-9 26 86     SPACE admet-9 26 87 passive passive ADJ admet-9 26 88     SPACE admet-9 26 89 membrane membrane NOUN admet-9 26 90     SPACE admet-9 26 91 partitioning partitioning NOUN admet-9 26 92 , , PUNCT admet-9 26 93     SPACE admet-9 26 94 influencing influence VERB admet-9 26 95     SPACE admet-9 26 96 permeability permeability NOUN admet-9 26 97     SPACE admet-9 26 98 opposite opposite NOUN admet-9 26 99     SPACE admet-9 26 100 to to ADP admet-9 26 101     SPACE admet-9 26 102 its its PRON admet-9 26 103     SPACE admet-9 26 104 effect effect NOUN admet-9 26 105     SPACE admet-9 26 106 on on ADP admet-9 26 107     SPACE admet-9 26 108 solubility solubility NOUN admet-9 26 109 . . PUNCT admet-9 26 110     SPACE admet-9 27 1 moreover moreover ADV admet-9 27 2 , , PUNCT admet-9 27 3     SPACE admet-9 27 4 if if SCONJ admet-9 27 5     SPACE admet-9 27 6 the the PRON admet-9 27 7     SPACE admet-9 27 8 in in ADP admet-9 27 9     SPACE admet-9 27 10 vitro vitro VERB admet-9 27 11     SPACE admet-9 27 12 metabolic metabolic NOUN admet-9 27 13     SPACE admet-9 27 14 stability stability NOUN admet-9 27 15     SPACE admet-9 27 16 data datum NOUN admet-9 27 17     SPACE admet-9 27 18 from from ADP admet-9 27 19     SPACE admet-9 27 20 phase phase NOUN admet-9 27 21     SPACE admet-9 27 22 i i PRON admet-9 27 23     SPACE admet-9 27 24 metabolism metabolism NOUN admet-9 27 25     SPACE admet-9 27 26 can can AUX admet-9 27 27 not not PART admet-9 27 28     SPACE admet-9 27 29 predict predict VERB admet-9 27 30     SPACE admet-9 27 31 in in ADP admet-9 27 32     SPACE admet-9 27 33 vivo vivo ADJ admet-9 27 34     SPACE admet-9 27 35 hepatic hepatic NOUN admet-9 27 36     SPACE admet-9 27 37 plasma plasma NOUN admet-9 27 38     SPACE admet-9 27 39 clearance clearance NOUN admet-9 27 40 , , PUNCT admet-9 27 41     SPACE admet-9 27 42 the the DET admet-9 27 43     SPACE admet-9 27 44 phase phase NOUN admet-9 27 45     SPACE admet-9 27 46 ii ii NOUN admet-9 27 47     SPACE admet-9 27 48 in in ADP admet-9 27 49     SPACE admet-9 27 50 vitro vitro VERB admet-9 27 51     SPACE admet-9 27 52 metabolism metabolism NOUN admet-9 27 53     SPACE admet-9 27 54 in in ADP admet-9 27 55     SPACE admet-9 27 56 hepatocytes hepatocyte NOUN admet-9 27 57     SPACE admet-9 27 58 and and CCONJ admet-9 27 59     SPACE admet-9 27 60 even even ADV admet-9 27 61     SPACE admet-9 27 62 hepatic hepatic ADJ admet-9 27 63     SPACE admet-9 27 64 transporters transporter NOUN admet-9 27 65     SPACE admet-9 27 66 such such ADJ admet-9 27 67     SPACE admet-9 27 68 as as ADP admet-9 27 69     SPACE admet-9 27 70 oatp1b1 oatp1b1 NOUN admet-9 27 71     SPACE admet-9 27 72 are be AUX admet-9 27 73     SPACE admet-9 27 74 then then ADV admet-9 27 75     SPACE admet-9 27 76 necessary necessary ADJ admet-9 27 77     SPACE admet-9 27 78 to to PART admet-9 27 79     SPACE admet-9 27 80 find find VERB admet-9 27 81     SPACE admet-9 27 82 the the DET admet-9 27 83     SPACE admet-9 27 84 relevant relevant NOUN admet-9 27 85     SPACE admet-9 27 86 in in ADP admet-9 27 87     SPACE admet-9 27 88 vitro vitro VERB admet-9 27 89     SPACE admet-9 27 90 models model NOUN admet-9 27 91     SPACE admet-9 27 92 for for ADP admet-9 27 93     SPACE admet-9 27 94 in in ADP admet-9 27 95     SPACE admet-9 27 96 vivo vivo NOUN admet-9 27 97     SPACE admet-9 27 98 metabolism metabolism NOUN admet-9 27 99     SPACE admet-9 27 100 prediction prediction NOUN admet-9 27 101     SPACE admet-9 27 102 to to PART admet-9 27 103     SPACE admet-9 27 104 drive drive VERB admet-9 27 105     SPACE admet-9 27 106 chemists chemist NOUN admet-9 27 107     SPACE admet-9 27 108 to to PART admet-9 27 109     SPACE admet-9 27 110 design design VERB admet-9 27 111     SPACE admet-9 27 112 and and CCONJ admet-9 27 113     SPACE admet-9 27 114 make make VERB admet-9 27 115     SPACE admet-9 27 116 more more ADJ admet-9 27 117     SPACE admet-9 27 118 potent potent NOUN admet-9 27 119     SPACE admet-9 27 120 and and CCONJ admet-9 27 121     SPACE admet-9 27 122 selective selective ADJ admet-9 27 123     SPACE admet-9 27 124 compounds compound NOUN admet-9 27 125     SPACE admet-9 27 126 with with ADP admet-9 27 127     SPACE admet-9 27 128 improved improve VERB admet-9 27 129     SPACE admet-9 27 130 pk pk NOUN admet-9 27 131     SPACE admet-9 27 132 profiles profile NOUN admet-9 27 133 . . PUNCT admet-9 27 134     SPACE admet-9 28 1 even even ADV admet-9 28 2     SPACE admet-9 28 3 at at ADP admet-9 28 4     SPACE admet-9 28 5 the the DET admet-9 28 6     SPACE admet-9 28 7 very very ADV admet-9 28 8     SPACE admet-9 28 9 early early ADJ admet-9 28 10     SPACE admet-9 28 11 stage stage NOUN admet-9 28 12     SPACE admet-9 28 13 of of ADP admet-9 28 14     SPACE admet-9 28 15 hit‐to‐lead hit‐to‐lead ADJ admet-9 28 16 , , PUNCT admet-9 28 17     SPACE admet-9 28 18 selective selective NOUN admet-9 28 19     SPACE admet-9 28 20 in in ADP admet-9 28 21     SPACE admet-9 28 22 vivo vivo NOUN admet-9 28 23     SPACE admet-9 28 24 pk pk NOUN admet-9 28 25     SPACE admet-9 28 26 studies study NOUN admet-9 28 27     SPACE admet-9 28 28 are be AUX admet-9 28 29     SPACE admet-9 28 30 valuable valuable ADJ admet-9 28 31     SPACE admet-9 28 32 to to PART admet-9 28 33     SPACE admet-9 28 34 confirm confirm VERB admet-9 28 35     SPACE admet-9 28 36 whether whether SCONJ admet-9 28 37     SPACE admet-9 28 38 the the DET admet-9 28 39     SPACE admet-9 28 40 applied apply VERB admet-9 28 41     SPACE admet-9 28 42 in in ADP admet-9 28 43     SPACE admet-9 28 44 vitro vitro VERB admet-9 28 45     SPACE admet-9 28 46 assays assay NOUN admet-9 28 47     SPACE admet-9 28 48 ( ( PUNCT admet-9 28 49 in in ADP admet-9 28 50     SPACE admet-9 28 51 vitro vitro VERB admet-9 28 52     SPACE admet-9 28 53 metabolism metabolism NOUN admet-9 28 54     SPACE admet-9 28 55 and and CCONJ admet-9 28 56     SPACE admet-9 28 57 absorption absorption NOUN admet-9 28 58 ) ) PUNCT admet-9 28 59     SPACE admet-9 28 60 can can AUX admet-9 28 61     SPACE admet-9 28 62 serve serve VERB admet-9 28 63     SPACE admet-9 28 64 as as ADP admet-9 28 65     SPACE admet-9 28 66 good good ADJ admet-9 28 67     SPACE admet-9 28 68 predictive predictive ADJ admet-9 28 69     SPACE admet-9 28 70 models model NOUN admet-9 28 71     SPACE admet-9 28 72 for for ADP admet-9 28 73     SPACE admet-9 28 74 in in ADP admet-9 28 75     SPACE admet-9 28 76 vivo vivo NOUN admet-9 28 77     SPACE admet-9 28 78 pk pk NOUN admet-9 28 79     SPACE admet-9 28 80 in in ADP admet-9 28 81     SPACE admet-9 28 82 terms term NOUN admet-9 28 83     SPACE admet-9 28 84 of of ADP admet-9 28 85     SPACE admet-9 28 86 plasma plasma NOUN admet-9 28 87     SPACE admet-9 28 88 clearance clearance NOUN admet-9 28 89     SPACE admet-9 28 90 and and CCONJ admet-9 28 91     SPACE admet-9 28 92 bioavailability bioavailability NOUN admet-9 28 93 . . PUNCT admet-9 28 94     SPACE admet-9 28 95 in in ADP admet-9 28 96     SPACE admet-9 28 97 some some DET admet-9 28 98     SPACE admet-9 28 99 circumstances circumstance NOUN admet-9 28 100 , , PUNCT admet-9 28 101     SPACE admet-9 28 102 if if SCONJ admet-9 28 103     SPACE admet-9 28 104 both both DET admet-9 28 105     SPACE admet-9 28 106 in in ADP admet-9 28 107     SPACE admet-9 28 108 vitro vitro VERB admet-9 28 109     SPACE admet-9 28 110 liver liver NOUN admet-9 28 111     SPACE admet-9 28 112 microsomes microsome NOUN admet-9 28 113     SPACE admet-9 28 114 and and CCONJ admet-9 28 115     SPACE admet-9 28 116 hepatocyte hepatocyte NOUN admet-9 28 117     SPACE admet-9 28 118 models model NOUN admet-9 28 119     SPACE admet-9 28 120 might might AUX admet-9 28 121     SPACE admet-9 28 122 not not PART admet-9 28 123     SPACE admet-9 28 124 predict predict VERB admet-9 28 125     SPACE admet-9 28 126 well well ADV admet-9 28 127     SPACE admet-9 28 128 in in ADP admet-9 28 129     SPACE admet-9 28 130 vivo vivo ADJ admet-9 28 131     SPACE admet-9 28 132 metabolism metabolism NOUN admet-9 28 133 , , PUNCT admet-9 28 134     SPACE admet-9 28 135 more more ADJ admet-9 28 136     SPACE admet-9 28 137 extensive extensive ADJ admet-9 28 138     SPACE admet-9 28 139 in in ADP admet-9 28 140     SPACE admet-9 28 141 vivo vivo NOUN admet-9 28 142     SPACE admet-9 28 143 pk pk NOUN admet-9 28 144     SPACE admet-9 28 145 studies study NOUN admet-9 28 146     SPACE admet-9 28 147 have have VERB admet-9 28 148     SPACE admet-9 28 149 to to PART admet-9 28 150     SPACE admet-9 28 151 be be AUX admet-9 28 152     SPACE admet-9 28 153 performed perform VERB admet-9 28 154     SPACE admet-9 28 155 as as ADP admet-9 28 156     SPACE admet-9 28 157 a a DET admet-9 28 158     SPACE admet-9 28 159 result result NOUN admet-9 28 160     SPACE admet-9 28 161 of of ADP admet-9 28 162     SPACE admet-9 28 163 poor poor ADJ admet-9 28 164     SPACE admet-9 28 165 in in ADP admet-9 28 166     SPACE admet-9 28 167 vitro vitro VERB admet-9 28 168     SPACE admet-9 28 169 and and CCONJ admet-9 28 170     SPACE admet-9 28 171 in in ADP admet-9 28 172     SPACE admet-9 28 173 vivo vivo NOUN admet-9 28 174     SPACE admet-9 28 175 correlations correlation NOUN admet-9 28 176     SPACE admet-9 28 177 based base VERB admet-9 28 178     SPACE admet-9 28 179 on on ADP admet-9 28 180     SPACE admet-9 28 181 evaluations evaluation NOUN admet-9 28 182     SPACE admet-9 28 183 by by ADP admet-9 28 184     SPACE admet-9 28 185 a a DET admet-9 28 186     SPACE admet-9 28 187 simplified simplified ADJ admet-9 28 188     SPACE admet-9 28 189 well‐stirred well‐stirred ADJ admet-9 28 190     SPACE admet-9 28 191 model model NOUN admet-9 28 192 . . PUNCT admet-9 28 193     SPACE admet-9 29 1 a a DET admet-9 29 2     SPACE admet-9 29 3 clear clear ADJ admet-9 29 4     SPACE admet-9 29 5 structure‐activity structure‐activity NOUN admet-9 29 6     SPACE admet-9 29 7 relationship relationship NOUN admet-9 29 8     SPACE admet-9 29 9 ( ( PUNCT admet-9 29 10 sar)/adme sar)/adme NOUN admet-9 29 11     SPACE admet-9 29 12 certainly certainly ADV admet-9 29 13     SPACE admet-9 29 14 facilitates facilitate VERB admet-9 29 15     SPACE admet-9 29 16 the the DET admet-9 29 17     SPACE admet-9 29 18 design design NOUN admet-9 29 19     SPACE admet-9 29 20 of of ADP admet-9 29 21     SPACE admet-9 29 22 new new ADJ admet-9 29 23     SPACE admet-9 29 24 compounds compound NOUN admet-9 29 25 . . PUNCT admet-9 29 26     SPACE admet-9 30 1 for for ADP admet-9 30 2     SPACE admet-9 30 3 the the DET admet-9 30 4     SPACE admet-9 30 5 drug drug NOUN admet-9 30 6     SPACE admet-9 30 7 absorption absorption NOUN admet-9 30 8     SPACE admet-9 30 9 evaluations evaluation NOUN admet-9 30 10 , , PUNCT admet-9 30 11     SPACE admet-9 30 12 there there PRON admet-9 30 13     SPACE admet-9 30 14 are be AUX admet-9 30 15     SPACE admet-9 30 16 three three NUM admet-9 30 17     SPACE admet-9 30 18 commonly commonly ADV admet-9 30 19     SPACE admet-9 30 20 used use VERB admet-9 30 21     SPACE admet-9 30 22 models model NOUN admet-9 30 23 , , PUNCT admet-9 30 24     SPACE admet-9 30 25 such such ADJ admet-9 30 26     SPACE admet-9 30 27 as as ADP admet-9 30 28     SPACE admet-9 30 29 pampa pampa NOUN admet-9 30 30 , , PUNCT admet-9 30 31     SPACE admet-9 30 32 and and CCONJ admet-9 30 33     SPACE admet-9 30 34 caco‐2 caco‐2 PROPN admet-9 30 35     SPACE admet-9 30 36 and and CCONJ admet-9 30 37     SPACE admet-9 30 38 mdck mdck ADJ admet-9 30 39     SPACE admet-9 30 40 permeability permeability NOUN admet-9 30 41 . . PUNCT admet-9 30 42     SPACE admet-9 30 43 from from ADP admet-9 30 44     SPACE admet-9 30 45 the the DET admet-9 30 46     SPACE admet-9 30 47 cost cost NOUN admet-9 30 48     SPACE admet-9 30 49 point point NOUN admet-9 30 50     SPACE admet-9 30 51 of of ADP admet-9 30 52     SPACE admet-9 30 53 view view NOUN admet-9 30 54 , , PUNCT admet-9 30 55     SPACE admet-9 30 56 the the DET admet-9 30 57     SPACE admet-9 30 58 pampa pampa NOUN admet-9 30 59     SPACE admet-9 30 60 membrane membrane NOUN admet-9 30 61     SPACE admet-9 30 62 permeability permeability NOUN admet-9 30 63     SPACE admet-9 30 64 assay assay VERB admet-9 30 65     SPACE admet-9 30 66 is be AUX admet-9 30 67     SPACE admet-9 30 68 the the DET admet-9 30 69     SPACE admet-9 30 70 most most ADJ admet-9 30 71     SPACE admet-9 30 72 cost‐effective cost‐effective ADJ admet-9 30 73     SPACE admet-9 30 74 among among ADP admet-9 30 75     SPACE admet-9 30 76 these these DET admet-9 30 77     SPACE admet-9 30 78 three three NUM admet-9 30 79     SPACE admet-9 30 80 in in ADP admet-9 30 81     SPACE admet-9 30 82 vitro vitro VERB admet-9 30 83     SPACE admet-9 30 84 models model NOUN admet-9 30 85 , , PUNCT admet-9 30 86     SPACE admet-9 30 87 with with ADP admet-9 30 88     SPACE admet-9 30 89 a a DET admet-9 30 90     SPACE admet-9 30 91 fast fast ADJ admet-9 30 92     SPACE admet-9 30 93 turnaround turnaround NOUN admet-9 30 94 , , PUNCT admet-9 30 95     SPACE admet-9 30 96 while while SCONJ admet-9 30 97     SPACE admet-9 30 98 the the DET admet-9 30 99     SPACE admet-9 30 100 caco‐2 caco‐2 PROPN admet-9 30 101     SPACE admet-9 30 102 and and CCONJ admet-9 30 103     SPACE admet-9 30 104 mdck‐mdr1 mdck‐mdr1 NUM admet-9 30 105     SPACE admet-9 30 106 models model NOUN admet-9 30 107     SPACE admet-9 30 108 can can AUX admet-9 30 109     SPACE admet-9 30 110 offer offer VERB admet-9 30 111     SPACE admet-9 30 112 more more ADJ admet-9 30 113     SPACE admet-9 30 114 accurate accurate ADJ admet-9 30 115     SPACE admet-9 30 116 absorption absorption NOUN admet-9 30 117     SPACE admet-9 30 118 prediction prediction NOUN admet-9 30 119     SPACE admet-9 30 120 as as ADV admet-9 30 121     SPACE admet-9 30 122 well well ADV admet-9 30 123     SPACE admet-9 30 124 as as SCONJ admet-9 30 125     SPACE admet-9 30 126 allow allow VERB admet-9 30 127     SPACE admet-9 30 128 efflux efflux NOUN admet-9 30 129     SPACE admet-9 30 130 and and CCONJ admet-9 30 131     SPACE admet-9 30 132 transporter transporter NOUN admet-9 30 133     SPACE admet-9 30 134 studies study NOUN admet-9 30 135     SPACE admet-9 30 136 for for ADP admet-9 30 137     SPACE admet-9 30 138 substrate substrate NOUN admet-9 30 139     SPACE admet-9 30 140 and and CCONJ admet-9 30 141     SPACE admet-9 30 142 inhibition inhibition NOUN admet-9 30 143     SPACE admet-9 30 144 identification identification NOUN admet-9 30 145 . . PUNCT admet-9 30 146             SPACE admet-9 31 1 traditionally traditionally ADV admet-9 31 2 , , PUNCT admet-9 31 3     SPACE admet-9 31 4 the the DET admet-9 31 5     SPACE admet-9 31 6 cyp cyp ADJ admet-9 31 7     SPACE admet-9 31 8 inhibition inhibition NOUN admet-9 31 9     SPACE admet-9 31 10 study study NOUN admet-9 31 11     SPACE admet-9 31 12 is be AUX admet-9 31 13     SPACE admet-9 31 14 conducted conduct VERB admet-9 31 15     SPACE admet-9 31 16 at at ADP admet-9 31 17     SPACE admet-9 31 18 a a DET admet-9 31 19     SPACE admet-9 31 20 late late ADJ admet-9 31 21     SPACE admet-9 31 22 stage stage NOUN admet-9 31 23 , , PUNCT admet-9 31 24     SPACE admet-9 31 25 e.g. e.g. ADV admet-9 31 26 , , PUNCT admet-9 31 27     SPACE admet-9 31 28 from from ADP admet-9 31 29     SPACE admet-9 31 30 lead lead ADJ admet-9 31 31     SPACE admet-9 31 32 optimisation optimisation NOUN admet-9 31 33     SPACE admet-9 31 34 to to ADP admet-9 31 35     SPACE admet-9 31 36 cs cs PROPN admet-9 31 37 . . PUNCT admet-9 31 38     SPACE admet-9 31 39 this this PRON admet-9 31 40     SPACE admet-9 31 41 has have AUX admet-9 31 42     SPACE admet-9 31 43 been be AUX admet-9 31 44     SPACE admet-9 31 45 now now ADV admet-9 31 46     SPACE admet-9 31 47 moved move VERB admet-9 31 48     SPACE admet-9 31 49 to to ADP admet-9 31 50     SPACE admet-9 31 51 earlier early ADJ admet-9 31 52     SPACE admet-9 31 53 stages stage NOUN admet-9 31 54 , , PUNCT admet-9 31 55     SPACE admet-9 31 56 even even ADV admet-9 31 57     SPACE admet-9 31 58 hit‐to‐lead hit‐to‐lead ADV admet-9 31 59 . . PUNCT admet-9 31 60     SPACE admet-9 32 1 table table NOUN admet-9 32 2     SPACE admet-9 32 3 1 1 NUM admet-9 32 4     SPACE admet-9 32 5 shows show VERB admet-9 32 6     SPACE admet-9 32 7 a a DET admet-9 32 8     SPACE admet-9 32 9 general general ADJ admet-9 32 10     SPACE admet-9 32 11 decision decision NOUN admet-9 32 12     SPACE admet-9 32 13 tree tree NOUN admet-9 32 14     SPACE admet-9 32 15 on on ADP admet-9 32 16     SPACE admet-9 32 17 cyp cyp ADJ admet-9 32 18     SPACE admet-9 32 19 inhibition inhibition NOUN admet-9 32 20     SPACE admet-9 32 21 based base VERB admet-9 32 22     SPACE admet-9 32 23 on on ADP admet-9 32 24     SPACE admet-9 32 25 drug‐drug drug‐drug NOUN admet-9 32 26     SPACE admet-9 32 27 interaction interaction NOUN admet-9 32 28     SPACE admet-9 32 29 ( ( PUNCT admet-9 32 30 ddi ddi PROPN admet-9 32 31 ) ) PUNCT admet-9 32 32     SPACE admet-9 32 33 assessment assessment NOUN admet-9 32 34 , , PUNCT admet-9 32 35     SPACE admet-9 32 36 with with ADP admet-9 32 37     SPACE admet-9 32 38 an an DET admet-9 32 39     SPACE admet-9 32 40 interpretation interpretation NOUN admet-9 32 41     SPACE admet-9 32 42 of of ADP admet-9 32 43     SPACE admet-9 32 44 potential potential NOUN admet-9 32 45     SPACE admet-9 32 46 for for ADP admet-9 32 47     SPACE admet-9 32 48 in in ADP admet-9 32 49     SPACE admet-9 32 50 vivo vivo NOUN admet-9 32 51     SPACE admet-9 32 52 inhibition inhibition NOUN admet-9 32 53     SPACE admet-9 32 54 ( ( PUNCT admet-9 32 55 derived derive VERB admet-9 32 56     SPACE admet-9 32 57 from from ADP admet-9 32 58     SPACE admet-9 32 59 fda fda PROPN admet-9 32 60     SPACE admet-9 32 61 guidance guidance NOUN admet-9 32 62     SPACE admet-9 32 63 for for ADP admet-9 32 64     SPACE admet-9 32 65 industry industry NOUN admet-9 32 66 : : PUNCT admet-9 32 67     SPACE admet-9 32 68 drug drug NOUN admet-9 32 69     SPACE admet-9 32 70 interaction interaction NOUN admet-9 32 71     SPACE admet-9 32 72 studies study NOUN admet-9 32 73     SPACE admet-9 32 74 – – PUNCT admet-9 32 75     SPACE admet-9 32 76 study study NOUN admet-9 32 77     SPACE admet-9 32 78 design design NOUN admet-9 32 79 , , PUNCT admet-9 32 80     SPACE admet-9 32 81 data datum NOUN admet-9 32 82     SPACE admet-9 32 83 analysis analysis NOUN admet-9 32 84 , , PUNCT admet-9 32 85     SPACE admet-9 32 86 implications implication NOUN admet-9 32 87     SPACE admet-9 32 88 for for ADP admet-9 32 89     SPACE admet-9 32 90 dosing dose VERB admet-9 32 91 , , PUNCT admet-9 32 92     SPACE admet-9 32 93 and and CCONJ admet-9 32 94     SPACE admet-9 32 95 labeling labeling NOUN admet-9 32 96     SPACE admet-9 32 97 recommendations recommendation NOUN admet-9 32 98 ) ) PUNCT admet-9 32 99     SPACE admet-9 33 1 [ [ X admet-9 33 2 1 1 NUM admet-9 33 3 ] ] PUNCT admet-9 33 4 . . PUNCT admet-9 33 5     SPACE admet-9 34 1 an an DET admet-9 34 2     SPACE admet-9 34 3 estimated estimate VERB admet-9 34 4     SPACE admet-9 34 5 [ [ PUNCT admet-9 34 6 i]/ki i]/ki NOUN admet-9 34 7     SPACE admet-9 34 8 ratio ratio NOUN admet-9 34 9     SPACE admet-9 34 10 of of ADP admet-9 34 11     SPACE admet-9 34 12 greater great ADJ admet-9 34 13     SPACE admet-9 34 14 than than SCONJ admet-9 34 15     SPACE admet-9 34 16 0.1 0.1 NUM admet-9 34 17     SPACE admet-9 34 18 is be AUX admet-9 34 19     SPACE admet-9 34 20 considered consider VERB admet-9 34 21     SPACE admet-9 34 22 positive positive ADJ admet-9 34 23     SPACE admet-9 34 24 and and CCONJ admet-9 34 25     SPACE admet-9 34 26 a a DET admet-9 34 27     SPACE admet-9 34 28 follow‐up follow‐up NOUN admet-9 34 29     SPACE admet-9 34 30 in in ADP admet-9 34 31     SPACE admet-9 34 32 vivo vivo NOUN admet-9 34 33     SPACE admet-9 34 34 evaluation evaluation NOUN admet-9 34 35     SPACE admet-9 34 36 is be AUX admet-9 34 37     SPACE admet-9 34 38 recommended recommend VERB admet-9 34 39 . . PUNCT admet-9 34 40     SPACE admet-9 35 1 the the DET admet-9 35 2     SPACE admet-9 35 3 likelihood likelihood NOUN admet-9 35 4     SPACE admet-9 35 5 of of ADP admet-9 35 6     SPACE admet-9 35 7 an an PRON admet-9 35 8     SPACE admet-9 35 9 in in ADP admet-9 35 10     SPACE admet-9 35 11 vivo vivo NOUN admet-9 35 12     SPACE admet-9 35 13 interaction interaction NOUN admet-9 35 14     SPACE admet-9 35 15 is be AUX admet-9 35 16     SPACE admet-9 35 17 projected project VERB admet-9 35 18     SPACE admet-9 35 19 based base VERB admet-9 35 20     SPACE admet-9 35 21 on on ADP admet-9 35 22     SPACE admet-9 35 23 the the DET admet-9 35 24     SPACE admet-9 35 25 [ [ NOUN admet-9 35 26 i]/ki i]/ki NOUN admet-9 35 27     SPACE admet-9 35 28 ratio ratio NOUN admet-9 35 29     SPACE admet-9 35 30 where where SCONJ admet-9 35 31     SPACE admet-9 35 32 [ [ X admet-9 35 33 i i X admet-9 35 34 ] ] X admet-9 35 35     SPACE admet-9 35 36 represents represent VERB admet-9 35 37     SPACE admet-9 35 38 the the DET admet-9 35 39     SPACE admet-9 35 40 mean mean ADJ admet-9 35 41     SPACE admet-9 35 42 steady‐state steady‐state ADJ admet-9 35 43     SPACE admet-9 35 44 cmax cmax NOUN admet-9 35 45     SPACE admet-9 35 46 value value NOUN admet-9 35 47     SPACE admet-9 35 48 for for ADP admet-9 35 49     SPACE admet-9 35 50 total total ADJ admet-9 35 51     SPACE admet-9 35 52 drug drug NOUN admet-9 35 53     SPACE admet-9 35 54 ( ( PUNCT admet-9 35 55 bound bind VERB admet-9 35 56     SPACE admet-9 35 57 plus plus CCONJ admet-9 35 58     SPACE admet-9 35 59 unbound unbound NOUN admet-9 35 60 ) ) PUNCT admet-9 35 61     SPACE admet-9 35 62 following follow VERB admet-9 35 63     SPACE admet-9 35 64 administration administration NOUN admet-9 35 65     SPACE admet-9 35 66 of of ADP admet-9 35 67     SPACE admet-9 35 68 the the DET admet-9 35 69     SPACE admet-9 35 70 highest high ADJ admet-9 35 71     SPACE admet-9 35 72 proposed propose VERB admet-9 35 73     SPACE admet-9 35 74 clinical clinical PROPN admet-9 35 75     SPACE admet-9 35 76 dose dose PROPN admet-9 35 77 . . PUNCT admet-9 35 78     SPACE admet-9 36 1 as as ADP admet-9 36 2     SPACE admet-9 36 3 the the DET admet-9 36 4     SPACE admet-9 36 5 ratio ratio NOUN admet-9 36 6     SPACE admet-9 36 7 increases increase NOUN admet-9 36 8 , , PUNCT admet-9 36 9     SPACE admet-9 36 10 the the DET admet-9 36 11     SPACE admet-9 36 12 likelihood likelihood NOUN admet-9 36 13     SPACE admet-9 36 14 of of ADP admet-9 36 15     SPACE admet-9 36 16 an an DET admet-9 36 17     SPACE admet-9 36 18 interaction interaction NOUN admet-9 36 19     SPACE admet-9 36 20 increases increase NOUN admet-9 36 21 . . PUNCT admet-9 36 22     SPACE admet-9 37 1 also also ADV admet-9 37 2 , , PUNCT admet-9 37 3     SPACE admet-9 37 4 for for ADP admet-9 37 5     SPACE admet-9 37 6 cyp3a cyp3a NOUN admet-9 37 7     SPACE admet-9 37 8 inhibition inhibition NOUN admet-9 37 9 , , PUNCT admet-9 37 10     SPACE admet-9 37 11 two two NUM admet-9 37 12     SPACE admet-9 37 13 structurally structurally ADV admet-9 37 14     SPACE admet-9 37 15 unrelated unrelated ADJ admet-9 37 16     SPACE admet-9 37 17 substrates substrate NOUN admet-9 37 18     SPACE admet-9 37 19 should should AUX admet-9 37 20     SPACE admet-9 37 21 be be AUX admet-9 37 22     SPACE admet-9 37 23 evaluated evaluate VERB admet-9 37 24     SPACE admet-9 37 25 in in ADP admet-9 37 26     SPACE admet-9 37 27 vitro vitro X admet-9 37 28 . . PUNCT admet-9 37 29     SPACE admet-9 38 1 if if SCONJ admet-9 38 2     SPACE admet-9 38 3 one one NUM admet-9 38 4     SPACE admet-9 38 5 of of ADP admet-9 38 6     SPACE admet-9 38 7 the the DET admet-9 38 8     SPACE admet-9 38 9 two two NUM admet-9 38 10     SPACE admet-9 38 11 evaluations evaluation NOUN admet-9 38 12     SPACE admet-9 38 13 suggests suggest VERB admet-9 38 14     SPACE admet-9 38 15 a a DET admet-9 38 16     SPACE admet-9 38 17 potential potential ADJ admet-9 38 18     SPACE admet-9 38 19 interaction interaction NOUN admet-9 38 20     SPACE admet-9 38 21 ( ( PUNCT admet-9 38 22 i.e. i.e. X admet-9 38 23 , , PUNCT admet-9 38 24     SPACE admet-9 38 25 [ [ X admet-9 38 26 i]/ki i]/ki NOUN admet-9 38 27     SPACE admet-9 38 28 of of ADP admet-9 38 29     SPACE admet-9 38 30 more more ADJ admet-9 38 31     SPACE admet-9 38 32 than than ADP admet-9 38 33     SPACE admet-9 38 34 0.1 0.1 NUM admet-9 38 35 ) ) PUNCT admet-9 38 36 , , PUNCT admet-9 38 37     SPACE admet-9 38 38 an an DET admet-9 38 39     SPACE admet-9 38 40 in in ADP admet-9 38 41     SPACE admet-9 38 42 vivo vivo NOUN admet-9 38 43     SPACE admet-9 38 44 evaluation evaluation NOUN admet-9 38 45     SPACE admet-9 38 46 should should AUX admet-9 38 47     SPACE admet-9 38 48 be be AUX admet-9 38 49     SPACE admet-9 38 50 carried carry VERB admet-9 38 51     SPACE admet-9 38 52 out out ADP admet-9 38 53 . . PUNCT admet-9 38 54     SPACE admet-9 39 1 at at ADP admet-9 39 2     SPACE admet-9 39 3 the the DET admet-9 39 4     SPACE admet-9 39 5 earlier early ADV admet-9 39 6     SPACE admet-9 39 7 screening screen VERB admet-9 39 8     SPACE admet-9 39 9 stage stage NOUN admet-9 39 10 , , PUNCT admet-9 39 11     SPACE admet-9 39 12 ic50 ic50 PROPN admet-9 39 13     SPACE admet-9 39 14 by by ADP admet-9 39 15     SPACE admet-9 39 16 a a DET admet-9 39 17     SPACE admet-9 39 18 single‐point single‐point NOUN admet-9 39 19     SPACE admet-9 39 20 screening screening NOUN admet-9 39 21     SPACE admet-9 39 22 assay assay VERB admet-9 39 23 , , PUNCT admet-9 39 24     SPACE admet-9 39 25 which which PRON admet-9 39 26     SPACE admet-9 39 27 is be AUX admet-9 39 28     SPACE admet-9 39 29 a a DET admet-9 39 30     SPACE admet-9 39 31 more more ADJ admet-9 39 32     SPACE admet-9 39 33 cost‐effective cost‐effective ADJ admet-9 39 34     SPACE admet-9 39 35 approach approach NOUN admet-9 39 36     SPACE admet-9 39 37 with with ADP admet-9 39 38     SPACE admet-9 39 39 acceptably acceptably ADV admet-9 39 40     SPACE admet-9 39 41 good good ADJ admet-9 39 42     SPACE admet-9 39 43 correlation correlation NOUN admet-9 39 44     SPACE admet-9 39 45 with with ADP admet-9 39 46     SPACE admet-9 39 47 full full ADJ admet-9 39 48     SPACE admet-9 39 49 curve curve NOUN admet-9 39 50     SPACE admet-9 39 51 ic50 ic50 PROPN admet-9 39 52     SPACE admet-9 39 53 assay assay NOUN admet-9 39 54 , , PUNCT admet-9 39 55     SPACE admet-9 39 56 can can AUX admet-9 39 57     SPACE admet-9 39 58 be be AUX admet-9 39 59     SPACE admet-9 39 60 used use VERB admet-9 39 61     SPACE admet-9 39 62 for for ADP admet-9 39 63     SPACE admet-9 39 64 initial initial ADJ admet-9 39 65     SPACE admet-9 39 66 ddi ddi ADJ admet-9 39 67     SPACE admet-9 39 68 evaluation evaluation NOUN admet-9 39 69 . . PUNCT admet-9 39 70     SPACE admet-9 40 1 a a DET admet-9 40 2     SPACE admet-9 40 3 full full ADJ admet-9 40 4     SPACE admet-9 40 5 curve curve NOUN admet-9 40 6     SPACE admet-9 40 7 ic50 ic50 PROPN admet-9 40 8     SPACE admet-9 40 9 or or CCONJ admet-9 40 10     SPACE admet-9 40 11 ki ki PROPN admet-9 40 12     SPACE admet-9 40 13 determination determination NOUN admet-9 40 14     SPACE admet-9 40 15 can can AUX admet-9 40 16     SPACE admet-9 40 17 be be AUX admet-9 40 18     SPACE admet-9 40 19 utilised utilise VERB admet-9 40 20     SPACE admet-9 40 21 for for ADP admet-9 40 22     SPACE admet-9 40 23 ddi ddi ADJ admet-9 40 24     SPACE admet-9 40 25 assessment assessment NOUN admet-9 40 26     SPACE admet-9 40 27 at at ADP admet-9 40 28     SPACE admet-9 40 29 a a DET admet-9 40 30     SPACE admet-9 40 31 late late ADJ admet-9 40 32     SPACE admet-9 40 33 phase phase NOUN admet-9 40 34     SPACE admet-9 40 35 for for ADP admet-9 40 36     SPACE admet-9 40 37 candidates candidate NOUN admet-9 40 38     SPACE admet-9 40 39 such such ADJ admet-9 40 40     SPACE admet-9 40 41 as as ADV admet-9 40 42     SPACE admet-9 40 43 nmes nme NOUN admet-9 40 44 . . PUNCT admet-9 40 45     SPACE admet-9 41 1 although although SCONJ admet-9 41 2     SPACE admet-9 41 3 quantitative quantitative ADJ admet-9 41 4     SPACE admet-9 41 5 predictions prediction NOUN admet-9 41 6     SPACE admet-9 41 7 of of ADP admet-9 41 8     SPACE admet-9 41 9 in in ADP admet-9 41 10     SPACE admet-9 41 11 vivo vivo NOUN admet-9 41 12     SPACE admet-9 41 13 ddi ddi PROPN admet-9 41 14     SPACE admet-9 41 15 from from ADP admet-9 41 16     SPACE admet-9 41 17 in in ADP admet-9 41 18     SPACE admet-9 41 19 vitro vitro VERB admet-9 41 20     SPACE admet-9 41 21 studies study NOUN admet-9 41 22     SPACE admet-9 41 23 are be AUX admet-9 41 24     SPACE admet-9 41 25 not not PART admet-9 41 26     SPACE admet-9 41 27 possible possible ADJ admet-9 41 28 , , PUNCT admet-9 41 29     SPACE admet-9 41 30 rank rank NOUN admet-9 41 31     SPACE admet-9 41 32 order order NOUN admet-9 41 33     SPACE admet-9 41 34 across across ADP admet-9 41 35     SPACE admet-9 41 36 the the DET admet-9 41 37     SPACE admet-9 41 38 different different ADJ admet-9 41 39     SPACE admet-9 41 40 cyp cyp ADJ admet-9 41 41     SPACE admet-9 41 42 enzymes enzyme NOUN admet-9 41 43     SPACE admet-9 41 44 for for ADP admet-9 41 45     SPACE admet-9 41 46 the the DET admet-9 41 47     SPACE admet-9 41 48 same same ADJ admet-9 41 49     SPACE admet-9 41 50 drug drug NOUN admet-9 41 51     SPACE admet-9 41 52 may may AUX admet-9 41 53     SPACE admet-9 41 54 help help VERB admet-9 41 55     SPACE admet-9 41 56 prioritise prioritise ADJ admet-9 41 57     SPACE admet-9 41 58 in in ADP admet-9 41 59     SPACE admet-9 41 60 vivo vivo NOUN admet-9 41 61     SPACE admet-9 41 62 ddi ddi PROPN admet-9 41 63     SPACE admet-9 41 64 assessment assessment NOUN admet-9 41 65 . . PUNCT admet-9 41 66         SPACE admet-9 42 1 wan wan PROPN admet-9 42 2         SPACE admet-9 42 3 admet admet X admet-9 42 4     SPACE admet-9 42 5 & & CCONJ admet-9 42 6     SPACE admet-9 42 7 dmpk dmpk VERB admet-9 42 8     SPACE admet-9 42 9 1(3 1(3 NUM admet-9 42 10 ) ) PUNCT admet-9 42 11     SPACE admet-9 42 12 ( ( PUNCT admet-9 42 13 2013 2013 NUM admet-9 42 14 ) ) PUNCT admet-9 42 15     SPACE admet-9 42 16 19‐28 19‐28 NUM admet-9 42 17     SPACE admet-9 42 18 22 22 NUM admet-9 42 19             SPACE admet-9 42 20 table table NOUN admet-9 42 21     SPACE admet-9 42 22 1 1 NUM admet-9 42 23 : : PUNCT admet-9 42 24     SPACE admet-9 42 25 prediction prediction NOUN admet-9 42 26     SPACE admet-9 42 27 of of ADP admet-9 42 28     SPACE admet-9 42 29 clinical clinical ADJ admet-9 42 30     SPACE admet-9 42 31 relevance relevance NOUN admet-9 42 32     SPACE admet-9 42 33 of of ADP admet-9 42 34     SPACE admet-9 42 35 competitive competitive ADJ admet-9 42 36     SPACE admet-9 42 37 cyp cyp ADJ admet-9 42 38     SPACE admet-9 42 39 inhibition inhibition NOUN admet-9 42 40     SPACE admet-9 42 41 likelihood likelihood NOUN admet-9 42 42     SPACE admet-9 42 43 ic50 ic50 PROPN admet-9 42 44     SPACE admet-9 42 45 ( ( PUNCT admet-9 42 46 μm μm NUM admet-9 42 47 ) ) PUNCT admet-9 43 1 [ [ X admet-9 43 2 i]/ki i]/ki X admet-9 43 3 [ [ X admet-9 43 4 1 1 NUM admet-9 43 5 ] ] PUNCT admet-9 43 6 . . PUNCT admet-9 43 7     SPACE admet-9 43 8 likely likely ADJ admet-9 43 9     SPACE admet-9 43 10 < < X admet-9 43 11     SPACE admet-9 43 12 1 1 NUM admet-9 43 13 > > PUNCT admet-9 43 14     SPACE admet-9 43 15 1 1 NUM admet-9 43 16 possible possible ADJ admet-9 43 17     SPACE admet-9 43 18 1 1 NUM admet-9 43 19     SPACE admet-9 43 20 < < NOUN admet-9 43 21     SPACE admet-9 43 22 ic50 ic50 PROPN admet-9 43 23 < < PROPN admet-9 43 24 10 10 NUM admet-9 43 25 0.1 0.1 NUM admet-9 43 26     SPACE admet-9 43 27 < < X admet-9 44 1 [ [ X admet-9 44 2 i i X admet-9 44 3 ] ] X admet-9 44 4     SPACE admet-9 44 5 /ki /ki PRON admet-9 44 6     SPACE admet-9 44 7 < < X admet-9 44 8 1 1 NUM admet-9 44 9     SPACE admet-9 44 10 unlikely unlikely ADJ admet-9 44 11     SPACE admet-9 44 12 > > SYM admet-9 44 13     SPACE admet-9 44 14 10 10 NUM admet-9 44 15 < < NOUN admet-9 44 16     SPACE admet-9 44 17 0.1 0.1 NUM admet-9 45 1 [ [ X admet-9 45 2 i i X admet-9 45 3 ] ] X admet-9 45 4     SPACE admet-9 45 5 is be AUX admet-9 45 6     SPACE admet-9 45 7 the the DET admet-9 45 8     SPACE admet-9 45 9 concentration concentration NOUN admet-9 45 10     SPACE admet-9 45 11 of of ADP admet-9 45 12     SPACE admet-9 45 13 inhibitor inhibitor NOUN admet-9 45 14     SPACE admet-9 45 15 exposed expose VERB admet-9 45 16     SPACE admet-9 45 17 to to ADP admet-9 45 18     SPACE admet-9 45 19 the the DET admet-9 45 20     SPACE admet-9 45 21 active active ADJ admet-9 45 22     SPACE admet-9 45 23 site site NOUN admet-9 45 24     SPACE admet-9 45 25 of of ADP admet-9 45 26     SPACE admet-9 45 27 the the DET admet-9 45 28     SPACE admet-9 45 29 enzyme enzyme NOUN admet-9 45 30     SPACE admet-9 45 31 in in ADP admet-9 45 32     SPACE admet-9 45 33 vivo vivo NOUN admet-9 45 34 , , PUNCT admet-9 45 35         SPACE admet-9 45 36 ki ki NOUN admet-9 45 37     SPACE admet-9 45 38 is be AUX admet-9 45 39     SPACE admet-9 45 40 the the DET admet-9 45 41     SPACE admet-9 45 42 inhibition inhibition NOUN admet-9 45 43     SPACE admet-9 45 44 constant constant ADJ admet-9 45 45 , , PUNCT admet-9 45 46     SPACE admet-9 45 47 which which PRON admet-9 45 48     SPACE admet-9 45 49 can can AUX admet-9 45 50     SPACE admet-9 45 51 be be AUX admet-9 45 52     SPACE admet-9 45 53 obtained obtain VERB admet-9 45 54     SPACE admet-9 45 55 by by ADP admet-9 45 56     SPACE admet-9 45 57 a a DET admet-9 45 58     SPACE admet-9 45 59 full full ADJ admet-9 45 60     SPACE admet-9 45 61 curve curve NOUN admet-9 45 62     SPACE admet-9 45 63 ic50 ic50 PROPN admet-9 45 64     SPACE admet-9 45 65 assay assay VERB admet-9 45 66 , , PUNCT admet-9 45 67     SPACE admet-9 45 68 or or CCONJ admet-9 45 69     SPACE admet-9 45 70 roughly roughly ADV admet-9 45 71     SPACE admet-9 45 72 estimated estimate VERB admet-9 45 73     SPACE admet-9 45 74 from from ADP admet-9 45 75     SPACE admet-9 45 76 the the DET admet-9 45 77     SPACE admet-9 45 78 ic50 ic50 PROPN admet-9 45 79 , , PUNCT admet-9 45 80     SPACE admet-9 45 81 i.e. i.e. X admet-9 45 82 , , PUNCT admet-9 45 83     SPACE admet-9 45 84 ki≈ic50/2 ki≈ic50/2 ADJ admet-9 45 85         SPACE admet-9 45 86 similar similar ADJ admet-9 45 87     SPACE admet-9 45 88 studies study NOUN admet-9 45 89     SPACE admet-9 45 90 associated associate VERB admet-9 45 91     SPACE admet-9 45 92 with with SCONJ admet-9 45 93     SPACE admet-9 45 94 transporters transporter NOUN admet-9 45 95     SPACE admet-9 45 96 are be AUX admet-9 45 97     SPACE admet-9 45 98 needed need VERB admet-9 45 99     SPACE admet-9 45 100 to to PART admet-9 45 101     SPACE admet-9 45 102 identify identify VERB admet-9 45 103     SPACE admet-9 45 104 whether whether SCONJ admet-9 45 105     SPACE admet-9 45 106 the the DET admet-9 45 107     SPACE admet-9 45 108 nmes nme NOUN admet-9 45 109     SPACE admet-9 45 110 could could AUX admet-9 45 111     SPACE admet-9 45 112 be be AUX admet-9 45 113     SPACE admet-9 45 114 a a DET admet-9 45 115     SPACE admet-9 45 116 potential potential ADJ admet-9 45 117     SPACE admet-9 45 118 substrate substrate NOUN admet-9 45 119     SPACE admet-9 45 120 or or CCONJ admet-9 45 121     SPACE admet-9 45 122 inhibitor inhibitor NOUN admet-9 45 123     SPACE admet-9 45 124 for for ADP admet-9 45 125     SPACE admet-9 45 126 p‐gp p‐gp NOUN admet-9 45 127     SPACE admet-9 45 128 or or CCONJ admet-9 45 129     SPACE admet-9 45 130 other other ADJ admet-9 45 131     SPACE admet-9 45 132 important important ADJ admet-9 45 133     SPACE admet-9 45 134 transporters transporter NOUN admet-9 45 135     SPACE admet-9 45 136 for for ADP admet-9 45 137     SPACE admet-9 45 138 ddi ddi NOUN admet-9 45 139     SPACE admet-9 45 140 as as ADV admet-9 45 141     SPACE admet-9 45 142 early early ADV admet-9 45 143     SPACE admet-9 45 144 as as ADP admet-9 45 145     SPACE admet-9 45 146 possible possible ADJ admet-9 45 147 . . PUNCT admet-9 45 148     SPACE admet-9 45 149 more more ADJ admet-9 45 150     SPACE admet-9 45 151 complex complex ADJ admet-9 45 152     SPACE admet-9 45 153 decision‐making decision‐making NOUN admet-9 45 154     SPACE admet-9 45 155 trees tree NOUN admet-9 45 156     SPACE admet-9 45 157 and and CCONJ admet-9 45 158     SPACE admet-9 45 159 recommended recommend VERB admet-9 45 160     SPACE admet-9 45 161 models model NOUN admet-9 45 162     SPACE admet-9 45 163 for for ADP admet-9 45 164     SPACE admet-9 45 165 transporter‐mediated transporter‐mediated ADJ admet-9 45 166     SPACE admet-9 45 167 ddi ddi ADJ admet-9 45 168     SPACE admet-9 45 169 assessment assessment NOUN admet-9 45 170     SPACE admet-9 45 171 are be AUX admet-9 45 172     SPACE admet-9 45 173 outlined outline VERB admet-9 45 174     SPACE admet-9 45 175 in in ADP admet-9 45 176     SPACE admet-9 45 177 the the DET admet-9 45 178     SPACE admet-9 45 179 fda fda PROPN admet-9 45 180 ’s ’s NOUN admet-9 45 181     SPACE admet-9 45 182 new new ADJ admet-9 45 183     SPACE admet-9 45 184 guidance guidance NOUN admet-9 45 185     SPACE admet-9 45 186 on on ADP admet-9 45 187     SPACE admet-9 45 188 drug drug NOUN admet-9 45 189     SPACE admet-9 45 190 interaction interaction NOUN admet-9 45 191     SPACE admet-9 45 192 studies study NOUN admet-9 45 193 . . PUNCT admet-9 45 194     SPACE admet-9 46 1 it it PRON admet-9 46 2     SPACE admet-9 46 3 should should AUX admet-9 46 4     SPACE admet-9 46 5 be be AUX admet-9 46 6     SPACE admet-9 46 7 pointed point VERB admet-9 46 8     SPACE admet-9 46 9 out out ADP admet-9 46 10     SPACE admet-9 46 11 that that SCONJ admet-9 46 12     SPACE admet-9 46 13 the the DET admet-9 46 14     SPACE admet-9 46 15 fda fda PROPN admet-9 46 16     SPACE admet-9 46 17 has have AUX admet-9 46 18     SPACE admet-9 46 19 extended extend VERB admet-9 46 20     SPACE admet-9 46 21 ddi ddi PROPN admet-9 46 22     SPACE admet-9 46 23 guidance guidance NOUN admet-9 46 24     SPACE admet-9 46 25 from from ADP admet-9 46 26     SPACE admet-9 46 27 the the DET admet-9 46 28     SPACE admet-9 46 29 2006 2006 NUM admet-9 46 30     SPACE admet-9 46 31 draft draft NOUN admet-9 46 32 , , PUNCT admet-9 46 33     SPACE admet-9 46 34 with with ADP admet-9 46 35     SPACE admet-9 46 36 52 52 NUM admet-9 46 37     SPACE admet-9 46 38 pages page NOUN admet-9 46 39 , , PUNCT admet-9 46 40     SPACE admet-9 46 41 to to ADP admet-9 46 42     SPACE admet-9 46 43 the the DET admet-9 46 44     SPACE admet-9 46 45 current current NOUN admet-9 46 46     SPACE admet-9 46 47 75 75 NUM admet-9 46 48     SPACE admet-9 46 49 pages page NOUN admet-9 46 50     SPACE admet-9 46 51 ( ( PUNCT admet-9 46 52 issued issue VERB admet-9 46 53     SPACE admet-9 46 54 in in ADP admet-9 46 55     SPACE admet-9 46 56 2012 2012 NUM admet-9 46 57 ) ) PUNCT admet-9 46 58 , , PUNCT admet-9 46 59     SPACE admet-9 46 60 reflecting reflect VERB admet-9 46 61     SPACE admet-9 46 62 the the DET admet-9 46 63     SPACE admet-9 46 64 importance importance NOUN admet-9 46 65     SPACE admet-9 46 66 and and CCONJ admet-9 46 67     SPACE admet-9 46 68 complexity complexity NOUN admet-9 46 69     SPACE admet-9 46 70 of of ADP admet-9 46 71     SPACE admet-9 46 72 drug drug NOUN admet-9 46 73     SPACE admet-9 46 74 interaction interaction NOUN admet-9 46 75     SPACE admet-9 46 76 studies study NOUN admet-9 46 77     SPACE admet-9 46 78 among among ADP admet-9 46 79     SPACE admet-9 46 80 the the DET admet-9 46 81     SPACE admet-9 46 82 dmpk dmpk NOUN admet-9 46 83     SPACE admet-9 47 1 [ [ X admet-9 47 2 1,2 1,2 NUM admet-9 47 3 ] ] PUNCT admet-9 47 4 . . PUNCT admet-9 47 5     SPACE admet-9 48 1 this this PRON admet-9 48 2     SPACE admet-9 48 3 is be AUX admet-9 48 4     SPACE admet-9 48 5 attributed attribute VERB admet-9 48 6     SPACE admet-9 48 7 to to ADP admet-9 48 8     SPACE admet-9 48 9 the the DET admet-9 48 10     SPACE admet-9 48 11 high high ADJ admet-9 48 12     SPACE admet-9 48 13 percentage percentage NOUN admet-9 48 14     SPACE admet-9 48 15 of of ADP admet-9 48 16     SPACE admet-9 48 17 drug drug NOUN admet-9 48 18     SPACE admet-9 48 19 failures failure NOUN admet-9 48 20     SPACE admet-9 48 21 caused cause VERB admet-9 48 22     SPACE admet-9 48 23 by by ADP admet-9 48 24     SPACE admet-9 48 25 ddi ddi PROPN admet-9 48 26 . . PUNCT admet-9 48 27         SPACE admet-9 48 28 another another DET admet-9 48 29     SPACE admet-9 48 30 important important ADJ admet-9 48 31     SPACE admet-9 48 32 aspect aspect NOUN admet-9 48 33     SPACE admet-9 48 34 includes include VERB admet-9 48 35     SPACE admet-9 48 36 the the DET admet-9 48 37     SPACE admet-9 48 38 drug drug NOUN admet-9 48 39     SPACE admet-9 48 40 metabolite metabolite NOUN admet-9 48 41     SPACE admet-9 48 42 identification identification NOUN admet-9 48 43     SPACE admet-9 48 44 and and CCONJ admet-9 48 45     SPACE admet-9 48 46 profiling profiling NOUN admet-9 48 47     SPACE admet-9 48 48 as as ADV admet-9 48 49     SPACE admet-9 48 50 well well ADV admet-9 48 51     SPACE admet-9 48 52 as as ADP admet-9 48 53     SPACE admet-9 48 54 metabolism metabolism NOUN admet-9 48 55     SPACE admet-9 48 56 pathways pathway NOUN admet-9 48 57     SPACE admet-9 48 58 in in ADP admet-9 48 59     SPACE admet-9 48 60 connection connection NOUN admet-9 48 61     SPACE admet-9 48 62 with with ADP admet-9 48 63     SPACE admet-9 48 64 cyp cyp ADJ admet-9 48 65     SPACE admet-9 48 66 metabolism metabolism NOUN admet-9 48 67     SPACE admet-9 48 68 enzyme enzyme NOUN admet-9 48 69     SPACE admet-9 48 70 identification identification NOUN admet-9 48 71     SPACE admet-9 48 72 ( ( PUNCT admet-9 48 73 the the DET admet-9 48 74     SPACE admet-9 48 75 so‐called so‐calle VERB admet-9 48 76     SPACE admet-9 48 77 cyp cyp ADJ admet-9 48 78     SPACE admet-9 48 79 i i PROPN admet-9 48 80 d d PROPN admet-9 48 81 ) ) PUNCT admet-9 48 82 . . PUNCT admet-9 48 83     SPACE admet-9 49 1 nowadays nowadays ADV admet-9 49 2 , , PUNCT admet-9 49 3     SPACE admet-9 49 4 the the DET admet-9 49 5     SPACE admet-9 49 6 rapid rapid ADJ admet-9 49 7     SPACE admet-9 49 8 metabolite metabolite NOUN admet-9 49 9     SPACE admet-9 49 10 identification identification NOUN admet-9 49 11     SPACE admet-9 49 12 ( ( PUNCT admet-9 49 13 metid metid NOUN admet-9 49 14 ) ) PUNCT admet-9 49 15     SPACE admet-9 49 16 at at ADP admet-9 49 17     SPACE admet-9 49 18 a a DET admet-9 49 19     SPACE admet-9 49 20 very very ADV admet-9 49 21     SPACE admet-9 49 22 early early ADJ admet-9 49 23     SPACE admet-9 49 24 stage stage NOUN admet-9 49 25     SPACE admet-9 49 26 has have AUX admet-9 49 27     SPACE admet-9 49 28 also also ADV admet-9 49 29     SPACE admet-9 49 30 become become VERB admet-9 49 31     SPACE admet-9 49 32 relatively relatively ADV admet-9 49 33     SPACE admet-9 49 34 easy easy ADJ admet-9 49 35 , , PUNCT admet-9 49 36     SPACE admet-9 49 37 such such ADJ admet-9 49 38     SPACE admet-9 49 39 as as ADP admet-9 49 40     SPACE admet-9 49 41 with with ADP admet-9 49 42     SPACE admet-9 49 43 metabolynx‐assisted metabolynx‐assisted ADJ admet-9 49 44     SPACE admet-9 49 45 structure structure NOUN admet-9 49 46     SPACE admet-9 49 47 identification identification NOUN admet-9 49 48     SPACE admet-9 49 49 software software NOUN admet-9 49 50 , , PUNCT admet-9 49 51     SPACE admet-9 49 52 which which PRON admet-9 49 53     SPACE admet-9 49 54 is be AUX admet-9 49 55     SPACE admet-9 49 56 especially especially ADV admet-9 49 57     SPACE admet-9 49 58 necessary necessary ADJ admet-9 49 59     SPACE admet-9 49 60 for for ADP admet-9 49 61     SPACE admet-9 49 62 metabolically metabolically NOUN admet-9 49 63     SPACE admet-9 49 64 unstable unstable ADJ admet-9 49 65     SPACE admet-9 49 66 compounds compound NOUN admet-9 49 67 , , PUNCT admet-9 49 68     SPACE admet-9 49 69 whose whose DET admet-9 49 70     SPACE admet-9 49 71 biotransformation biotransformation NOUN admet-9 49 72     SPACE admet-9 49 73 can can AUX admet-9 49 74     SPACE admet-9 49 75 help help VERB admet-9 49 76     SPACE admet-9 49 77 chemists chemist NOUN admet-9 49 78     SPACE admet-9 49 79 understand understand VERB admet-9 49 80     SPACE admet-9 49 81 the the DET admet-9 49 82     SPACE admet-9 49 83 site site NOUN admet-9 49 84     SPACE admet-9 49 85 of of ADP admet-9 49 86     SPACE admet-9 49 87 metabolic metabolic NOUN admet-9 49 88     SPACE admet-9 49 89 liability liability NOUN admet-9 49 90 , , PUNCT admet-9 49 91     SPACE admet-9 49 92 for for ADP admet-9 49 93     SPACE admet-9 49 94 further further ADJ admet-9 49 95     SPACE admet-9 49 96 structure structure NOUN admet-9 49 97     SPACE admet-9 49 98 modification modification NOUN admet-9 49 99     SPACE admet-9 49 100 for for ADP admet-9 49 101     SPACE admet-9 49 102 a a DET admet-9 49 103     SPACE admet-9 49 104 desirable desirable ADJ admet-9 49 105     SPACE admet-9 49 106 metabolism metabolism NOUN admet-9 49 107     SPACE admet-9 49 108 profile profile NOUN admet-9 49 109 . . PUNCT admet-9 49 110     SPACE admet-9 50 1 with with ADP admet-9 50 2     SPACE admet-9 50 3 the the DET admet-9 50 4     SPACE admet-9 50 5 issuance issuance NOUN admet-9 50 6     SPACE admet-9 50 7 of of ADP admet-9 50 8     SPACE admet-9 50 9 the the DET admet-9 50 10     SPACE admet-9 50 11 fda fda PROPN admet-9 50 12 ’s ’s NOUN admet-9 50 13     SPACE admet-9 50 14 final final ADJ admet-9 50 15     SPACE admet-9 50 16 guidance guidance NOUN admet-9 50 17     SPACE admet-9 50 18 for for ADP admet-9 50 19     SPACE admet-9 50 20 industry industry NOUN admet-9 50 21     SPACE admet-9 50 22 on on ADP admet-9 50 23     SPACE admet-9 50 24 safety safety NOUN admet-9 50 25     SPACE admet-9 50 26 testing testing NOUN admet-9 50 27     SPACE admet-9 50 28 of of ADP admet-9 50 29     SPACE admet-9 50 30 drug drug NOUN admet-9 50 31     SPACE admet-9 50 32 metabolites metabolite NOUN admet-9 50 33     SPACE admet-9 50 34 ( ( PUNCT admet-9 50 35 mist mist NOUN admet-9 50 36 ) ) PUNCT admet-9 50 37 , , PUNCT admet-9 50 38     SPACE admet-9 50 39 there there PRON admet-9 50 40     SPACE admet-9 50 41 is be AUX admet-9 50 42     SPACE admet-9 50 43 increased increase VERB admet-9 50 44     SPACE admet-9 50 45 concern concern NOUN admet-9 50 46     SPACE admet-9 50 47 for for ADP admet-9 50 48     SPACE admet-9 50 49 obtaining obtain VERB admet-9 50 50     SPACE admet-9 50 51 metabolite metabolite NOUN admet-9 50 52     SPACE admet-9 50 53 data datum NOUN admet-9 50 54     SPACE admet-9 50 55 as as ADP admet-9 50 56     SPACE admet-9 50 57 early early ADV admet-9 50 58     SPACE admet-9 50 59 as as ADP admet-9 50 60     SPACE admet-9 50 61 possible possible ADJ admet-9 50 62     SPACE admet-9 50 63 in in ADP admet-9 50 64     SPACE admet-9 50 65 preclinical preclinical ADJ admet-9 50 66     SPACE admet-9 50 67 studies study NOUN admet-9 50 68 . . PUNCT admet-9 50 69     SPACE admet-9 51 1 the the DET admet-9 51 2     SPACE admet-9 51 3 discovery discovery NOUN admet-9 51 4     SPACE admet-9 51 5 of of ADP admet-9 51 6     SPACE admet-9 51 7 disproportionate disproportionate ADJ admet-9 51 8     SPACE admet-9 51 9 drug drug NOUN admet-9 51 10     SPACE admet-9 51 11 metabolites metabolite NOUN admet-9 51 12     SPACE admet-9 51 13 late late ADJ admet-9 51 14     SPACE admet-9 51 15 in in ADP admet-9 51 16     SPACE admet-9 51 17 drug drug NOUN admet-9 51 18     SPACE admet-9 51 19 development development NOUN admet-9 51 20     SPACE admet-9 51 21 can can AUX admet-9 51 22     SPACE admet-9 51 23 potentially potentially ADV admet-9 51 24     SPACE admet-9 51 25 cause cause VERB admet-9 51 26     SPACE admet-9 51 27 development development NOUN admet-9 51 28     SPACE admet-9 51 29 and and CCONJ admet-9 51 30     SPACE admet-9 51 31 market market NOUN admet-9 51 32     SPACE admet-9 51 33 delays delay NOUN admet-9 51 34 . . PUNCT admet-9 51 35     SPACE admet-9 52 1 as as SCONJ admet-9 52 2     SPACE admet-9 52 3 guided guide VERB admet-9 52 4     SPACE admet-9 52 5 in in ADP admet-9 52 6     SPACE admet-9 52 7 mist mist NOUN admet-9 52 8     SPACE admet-9 52 9 published publish VERB admet-9 52 10     SPACE admet-9 52 11 in in ADP admet-9 52 12     SPACE admet-9 52 13 2008 2008 NUM admet-9 52 14     SPACE admet-9 52 15 as as ADV admet-9 52 16     SPACE admet-9 52 17 well well ADV admet-9 52 18     SPACE admet-9 52 19 as as ADV admet-9 52 20     SPACE admet-9 52 21 in in ADP admet-9 52 22     SPACE admet-9 52 23 the the DET admet-9 52 24     SPACE admet-9 52 25 ich ich NOUN admet-9 52 26     SPACE admet-9 52 27 m3 m3 PROPN admet-9 52 28     SPACE admet-9 52 29 ( ( PUNCT admet-9 52 30 r2 r2 PROPN admet-9 52 31 ) ) PUNCT admet-9 52 32     SPACE admet-9 52 33 published publish VERB admet-9 52 34     SPACE admet-9 52 35 in in ADP admet-9 52 36     SPACE admet-9 52 37 2009 2009 NUM admet-9 52 38     SPACE admet-9 53 1 [ [ X admet-9 53 2 3,4 3,4 NUM admet-9 53 3 ] ] PUNCT admet-9 53 4 , , PUNCT admet-9 53 5     SPACE admet-9 53 6 if if SCONJ admet-9 53 7     SPACE admet-9 53 8 a a DET admet-9 53 9     SPACE admet-9 53 10 metabolite metabolite NOUN admet-9 53 11     SPACE admet-9 53 12 is be AUX admet-9 53 13     SPACE admet-9 53 14 a a DET admet-9 53 15     SPACE admet-9 53 16 unique unique ADJ admet-9 53 17     SPACE admet-9 53 18 human human ADJ admet-9 53 19     SPACE admet-9 53 20 metabolite metabolite NOUN admet-9 53 21 , , PUNCT admet-9 53 22     SPACE admet-9 53 23 or or CCONJ admet-9 53 24     SPACE admet-9 53 25 more more ADJ admet-9 53 26     SPACE admet-9 53 27 commonly commonly ADV admet-9 53 28 , , PUNCT admet-9 53 29     SPACE admet-9 53 30 if if SCONJ admet-9 53 31     SPACE admet-9 53 32 a a DET admet-9 53 33     SPACE admet-9 53 34 circulating circulate VERB admet-9 53 35     SPACE admet-9 53 36 metabolite metabolite NOUN admet-9 53 37     SPACE admet-9 53 38 is be AUX admet-9 53 39     SPACE admet-9 53 40 present present ADJ admet-9 53 41     SPACE admet-9 53 42 at at ADP admet-9 53 43     SPACE admet-9 53 44 disproportionately disproportionately ADV admet-9 53 45     SPACE admet-9 53 46 higher high ADJ admet-9 53 47     SPACE admet-9 53 48 levels level NOUN admet-9 53 49     SPACE admet-9 53 50 in in ADP admet-9 53 51     SPACE admet-9 53 52 humans human NOUN admet-9 53 53     SPACE admet-9 53 54 than than ADP admet-9 53 55     SPACE admet-9 53 56 in in ADP admet-9 53 57     SPACE admet-9 53 58 the the DET admet-9 53 59     SPACE admet-9 53 60 animal animal NOUN admet-9 53 61     SPACE admet-9 53 62 species specie NOUN admet-9 53 63     SPACE admet-9 53 64 used use VERB admet-9 53 65     SPACE admet-9 53 66 in in ADP admet-9 53 67     SPACE admet-9 53 68 toxicology toxicology NOUN admet-9 53 69     SPACE admet-9 53 70 studies study NOUN admet-9 53 71 , , PUNCT admet-9 53 72     SPACE admet-9 53 73 additional additional ADJ admet-9 53 74     SPACE admet-9 53 75 non‐clinical non‐clinical ADJ admet-9 53 76     SPACE admet-9 53 77 safety safety NOUN admet-9 53 78     SPACE admet-9 53 79 assessment assessment NOUN admet-9 53 80     SPACE admet-9 53 81 studies study NOUN admet-9 53 82     SPACE admet-9 53 83 may may AUX admet-9 53 84     SPACE admet-9 53 85 be be AUX admet-9 53 86     SPACE admet-9 53 87 required require VERB admet-9 53 88 . . PUNCT admet-9 53 89     SPACE admet-9 54 1 as as SCONJ admet-9 54 2     SPACE admet-9 54 3 exemplified exemplify VERB admet-9 54 4     SPACE admet-9 54 5 in in ADP admet-9 54 6     SPACE admet-9 54 7 figure figure NOUN admet-9 54 8     SPACE admet-9 54 9 2 2 NUM admet-9 54 10 , , PUNCT admet-9 54 11     SPACE admet-9 54 12 any any DET admet-9 54 13     SPACE admet-9 54 14 metabolites metabolite NOUN admet-9 54 15     SPACE admet-9 54 16 found find VERB admet-9 54 17     SPACE admet-9 54 18 to to PART admet-9 54 19     SPACE admet-9 54 20 be be AUX admet-9 54 21     SPACE admet-9 54 22 > > SYM admet-9 54 23 10 10 NUM admet-9 54 24 % % NOUN admet-9 54 25     SPACE admet-9 54 26 ( ( PUNCT admet-9 54 27 based base VERB admet-9 54 28     SPACE admet-9 54 29 on on ADP admet-9 54 30     SPACE admet-9 54 31 systemic systemic ADJ admet-9 54 32     SPACE admet-9 54 33 exposure exposure NOUN admet-9 54 34     SPACE admet-9 54 35 at at ADP admet-9 54 36     SPACE admet-9 54 37 steady steady ADJ admet-9 54 38     SPACE admet-9 54 39 state state NOUN admet-9 54 40 ) ) PUNCT admet-9 54 41     SPACE admet-9 54 42 of of ADP admet-9 54 43     SPACE admet-9 54 44 total total NOUN admet-9 54 45     SPACE admet-9 54 46 drug‐related drug‐relate VERB admet-9 54 47     SPACE admet-9 54 48 material material NOUN admet-9 54 49     SPACE admet-9 54 50 should should AUX admet-9 54 51     SPACE admet-9 54 52 then then ADV admet-9 54 53     SPACE admet-9 54 54 be be AUX admet-9 54 55     SPACE admet-9 54 56 monitored monitor VERB admet-9 54 57     SPACE admet-9 54 58 in in ADP admet-9 54 59     SPACE admet-9 54 60 repeating repeat VERB admet-9 54 61     SPACE admet-9 54 62 dose dose NOUN admet-9 54 63     SPACE admet-9 54 64 animal animal NOUN admet-9 54 65     SPACE admet-9 54 66 toxicology toxicology NOUN admet-9 54 67     SPACE admet-9 54 68 studies study NOUN admet-9 54 69     SPACE admet-9 54 70 to to PART admet-9 54 71     SPACE admet-9 54 72 determine determine VERB admet-9 54 73     SPACE admet-9 54 74 if if SCONJ admet-9 54 75     SPACE admet-9 54 76 they they PRON admet-9 54 77     SPACE admet-9 54 78 are be AUX admet-9 54 79     SPACE admet-9 54 80 present present ADJ admet-9 54 81     SPACE admet-9 54 82 at at ADP admet-9 54 83     SPACE admet-9 54 84 higher high ADJ admet-9 54 85     SPACE admet-9 54 86 levels level NOUN admet-9 54 87     SPACE admet-9 54 88 in in ADP admet-9 54 89     SPACE admet-9 54 90 other other ADJ admet-9 54 91     SPACE admet-9 54 92 species specie NOUN admet-9 54 93     SPACE admet-9 54 94 as as ADV admet-9 54 95     SPACE admet-9 54 96 well well ADV admet-9 54 97 . . PUNCT admet-9 54 98     SPACE admet-9 55 1 exceptions exception NOUN admet-9 55 2     SPACE admet-9 55 3 might might AUX admet-9 55 4     SPACE admet-9 55 5 be be AUX admet-9 55 6     SPACE admet-9 55 7 possible possible ADJ admet-9 55 8     SPACE admet-9 55 9 for for ADP admet-9 55 10     SPACE admet-9 55 11 lower‐risk lower‐risk NOUN admet-9 55 12     SPACE admet-9 55 13 metabolites metabolite NOUN admet-9 55 14 , , PUNCT admet-9 55 15     SPACE admet-9 55 16 such such ADJ admet-9 55 17     SPACE admet-9 55 18 as as ADP admet-9 55 19     SPACE admet-9 55 20 most most ADJ admet-9 55 21     SPACE admet-9 55 22 phase phase NOUN admet-9 55 23     SPACE admet-9 55 24 ii ii NOUN admet-9 55 25     SPACE admet-9 55 26 conjugated conjugate VERB admet-9 55 27     SPACE admet-9 55 28 metabolites metabolite NOUN admet-9 55 29 . . PUNCT admet-9 55 30     SPACE admet-9 56 1 if if SCONJ admet-9 56 2     SPACE admet-9 56 3 the the DET admet-9 56 4     SPACE admet-9 56 5 major major ADJ admet-9 56 6     SPACE admet-9 56 7 metabolite metabolite NOUN admet-9 56 8     SPACE admet-9 56 9 exposure exposure NOUN admet-9 56 10     SPACE admet-9 56 11 in in ADP admet-9 56 12     SPACE admet-9 56 13 at at ADP admet-9 56 14     SPACE admet-9 56 15 least least ADJ admet-9 56 16     SPACE admet-9 56 17 one one NUM admet-9 56 18     SPACE admet-9 56 19 species specie NOUN admet-9 56 20     SPACE admet-9 56 21 is be AUX admet-9 56 22     SPACE admet-9 56 23 greater great ADJ admet-9 56 24     SPACE admet-9 56 25 than than ADP admet-9 56 26     SPACE admet-9 56 27 in in ADP admet-9 56 28     SPACE admet-9 56 29 the the DET admet-9 56 30     SPACE admet-9 56 31 human human NOUN admet-9 56 32 , , PUNCT admet-9 56 33     SPACE admet-9 56 34 then then ADV admet-9 56 35     SPACE admet-9 56 36 no no PRON admet-9 56 37     SPACE admet-9 56 38 additional additional ADJ admet-9 56 39     SPACE admet-9 56 40 safety safety NOUN admet-9 56 41     SPACE admet-9 56 42 studies study NOUN admet-9 56 43     SPACE admet-9 56 44 of of ADP admet-9 56 45     SPACE admet-9 56 46 the the DET admet-9 56 47     SPACE admet-9 56 48 metabolite metabolite NOUN admet-9 56 49     SPACE admet-9 56 50 are be AUX admet-9 56 51     SPACE admet-9 56 52 needed need VERB admet-9 56 53 . . PUNCT admet-9 56 54     SPACE admet-9 57 1 it it PRON admet-9 57 2     SPACE admet-9 57 3 should should AUX admet-9 57 4     SPACE admet-9 57 5 be be AUX admet-9 57 6     SPACE admet-9 57 7 noted note VERB admet-9 57 8     SPACE admet-9 57 9 that that SCONJ admet-9 57 10     SPACE admet-9 57 11 the the DET admet-9 57 12     SPACE admet-9 57 13 metabolite metabolite NOUN admet-9 57 14     SPACE admet-9 57 15 decision decision NOUN admet-9 57 16     SPACE admet-9 57 17 tree tree NOUN admet-9 57 18     SPACE admet-9 57 19 shown show VERB admet-9 57 20     SPACE admet-9 57 21 in in ADP admet-9 57 22     SPACE admet-9 57 23 figure figure NOUN admet-9 57 24     SPACE admet-9 57 25 2 2 NUM admet-9 57 26     SPACE admet-9 57 27 is be AUX admet-9 57 28     SPACE admet-9 57 29 only only ADV admet-9 57 30     SPACE admet-9 57 31 a a DET admet-9 57 32     SPACE admet-9 57 33 suggestion suggestion NOUN admet-9 57 34     SPACE admet-9 57 35 or or CCONJ admet-9 57 36     SPACE admet-9 57 37 recommendation recommendation NOUN admet-9 57 38 , , PUNCT admet-9 57 39     SPACE admet-9 57 40 with with ADP admet-9 57 41     SPACE admet-9 57 42 an an DET admet-9 57 43     SPACE admet-9 57 44 approximate approximate ADJ admet-9 57 45     SPACE admet-9 57 46 10 10 NUM admet-9 57 47 % % NOUN admet-9 57 48     SPACE admet-9 57 49 cut‐off cut‐off NOUN admet-9 57 50 , , PUNCT admet-9 57 51     SPACE admet-9 57 52 which which PRON admet-9 57 53     SPACE admet-9 57 54 does do AUX admet-9 57 55     SPACE admet-9 57 56 not not PART admet-9 57 57     SPACE admet-9 57 58 necessarily necessarily ADV admet-9 57 59     SPACE admet-9 57 60 mean mean VERB admet-9 57 61     SPACE admet-9 57 62 a a DET admet-9 57 63     SPACE admet-9 57 64 metabolite metabolite NOUN admet-9 57 65     SPACE admet-9 57 66 testing testing NOUN admet-9 57 67     SPACE admet-9 57 68 safety safety NOUN admet-9 57 69     SPACE admet-9 57 70 guarantee guarantee NOUN admet-9 57 71 . . PUNCT admet-9 57 72     SPACE admet-9 58 1 for for ADP admet-9 58 2     SPACE admet-9 58 3 instance instance NOUN admet-9 58 4 , , PUNCT admet-9 58 5     SPACE admet-9 58 6 if if SCONJ admet-9 58 7     SPACE admet-9 58 8 a a DET admet-9 58 9     SPACE admet-9 58 10 drug drug NOUN admet-9 58 11     SPACE admet-9 58 12 shows show VERB admet-9 58 13     SPACE admet-9 58 14 a a DET admet-9 58 15     SPACE admet-9 58 16 low low ADJ admet-9 58 17     SPACE admet-9 58 18 predicted predict VERB admet-9 58 19     SPACE admet-9 58 20 efficacy efficacy NOUN admet-9 58 21     SPACE admet-9 58 22 dose dose PROPN admet-9 58 23     SPACE admet-9 58 24 ( ( PUNCT admet-9 58 25 10 10 NUM admet-9 58 26     SPACE admet-9 58 27 mg mg NOUN admet-9 58 28     SPACE admet-9 58 29 or or CCONJ admet-9 58 30     SPACE admet-9 58 31 lower low ADJ admet-9 58 32 ) ) PUNCT admet-9 58 33 , , PUNCT admet-9 58 34     SPACE admet-9 58 35 a a DET admet-9 58 36     SPACE admet-9 58 37 metabolite metabolite NOUN admet-9 58 38     SPACE admet-9 58 39 found find VERB admet-9 58 40     SPACE admet-9 58 41 to to PART admet-9 58 42     SPACE admet-9 58 43 be be AUX admet-9 58 44     SPACE admet-9 58 45 over over ADV admet-9 58 46     SPACE admet-9 58 47 10 10 NUM admet-9 58 48 % % NOUN admet-9 58 49     SPACE admet-9 58 50 of of ADP admet-9 58 51     SPACE admet-9 58 52 total total NOUN admet-9 58 53     SPACE admet-9 58 54 drug‐related drug‐relate VERB admet-9 58 55     SPACE admet-9 58 56 material material NOUN admet-9 58 57     SPACE admet-9 58 58 might might AUX admet-9 58 59     SPACE admet-9 58 60 not not PART admet-9 58 61     SPACE admet-9 58 62 require require VERB admet-9 58 63     SPACE admet-9 58 64 further further ADJ admet-9 58 65     SPACE admet-9 58 66 safety safety NOUN admet-9 58 67     SPACE admet-9 58 68 tests test NOUN admet-9 58 69 . . PUNCT admet-9 58 70     SPACE admet-9 59 1 in in ADP admet-9 59 2     SPACE admet-9 59 3 contrast contrast NOUN admet-9 59 4 , , PUNCT admet-9 59 5     SPACE admet-9 59 6 for for ADP admet-9 59 7     SPACE admet-9 59 8 a a DET admet-9 59 9     SPACE admet-9 59 10 highly highly ADV admet-9 59 11     SPACE admet-9 59 12 dosed dose VERB admet-9 59 13     SPACE admet-9 59 14 compound compound NOUN admet-9 59 15 , , PUNCT admet-9 59 16     SPACE admet-9 59 17 even even ADV admet-9 59 18     SPACE admet-9 59 19 if if SCONJ admet-9 59 20     SPACE admet-9 59 21 a a DET admet-9 59 22     SPACE admet-9 59 23 metabolite metabolite NOUN admet-9 59 24     SPACE admet-9 59 25 is be AUX admet-9 59 26     SPACE admet-9 59 27 lower low ADJ admet-9 59 28     SPACE admet-9 59 29 than than ADP admet-9 59 30     SPACE admet-9 59 31 10 10 NUM admet-9 59 32 % % NOUN admet-9 59 33     SPACE admet-9 59 34 of of ADP admet-9 59 35     SPACE admet-9 59 36 total total NOUN admet-9 59 37     SPACE admet-9 59 38 drug‐related drug‐related ADJ admet-9 59 39     SPACE admet-9 59 40 material material NOUN admet-9 59 41 , , PUNCT admet-9 59 42     SPACE admet-9 59 43 it it PRON admet-9 59 44     SPACE admet-9 59 45 could could AUX admet-9 59 46     SPACE admet-9 59 47 be be AUX admet-9 59 48     SPACE admet-9 59 49 toxic toxic ADJ admet-9 59 50 , , PUNCT admet-9 59 51     SPACE admet-9 59 52 especially especially ADV admet-9 59 53     SPACE admet-9 59 54 with with ADP admet-9 59 55     SPACE admet-9 59 56 accumulation accumulation NOUN admet-9 59 57     SPACE admet-9 59 58 of of ADP admet-9 59 59     SPACE admet-9 59 60 the the DET admet-9 59 61     SPACE admet-9 59 62 metabolite metabolite NOUN admet-9 59 63 . . PUNCT admet-9 59 64     SPACE admet-9 60 1 also also ADV admet-9 60 2 , , PUNCT admet-9 60 3     SPACE admet-9 60 4 a a DET admet-9 60 5     SPACE admet-9 60 6 reactive reactive NOUN admet-9 60 7     SPACE admet-9 60 8 metabolite metabolite NOUN admet-9 60 9     SPACE admet-9 60 10 might might AUX admet-9 60 11     SPACE admet-9 60 12 be be AUX admet-9 60 13     SPACE admet-9 60 14 toxic toxic ADJ admet-9 60 15     SPACE admet-9 60 16 at at ADP admet-9 60 17     SPACE admet-9 60 18 a a DET admet-9 60 19     SPACE admet-9 60 20 very very ADV admet-9 60 21     SPACE admet-9 60 22 low low ADJ admet-9 60 23     SPACE admet-9 60 24 concentration concentration NOUN admet-9 60 25 . . PUNCT admet-9 60 26     SPACE admet-9 61 1 overall overall ADV admet-9 61 2 , , PUNCT admet-9 61 3     SPACE admet-9 61 4 a a DET admet-9 61 5     SPACE admet-9 61 6 metabolite metabolite NOUN admet-9 61 7     SPACE admet-9 61 8 safety safety NOUN admet-9 61 9     SPACE admet-9 61 10 testing testing NOUN admet-9 61 11     SPACE admet-9 61 12 decision decision NOUN admet-9 61 13     SPACE admet-9 61 14 should should AUX admet-9 61 15     SPACE admet-9 61 16 consider consider VERB admet-9 61 17     SPACE admet-9 61 18 many many ADJ admet-9 61 19     SPACE admet-9 61 20 factors factor NOUN admet-9 61 21 , , PUNCT admet-9 61 22     SPACE admet-9 61 23 such such ADJ admet-9 61 24     SPACE admet-9 61 25 as as ADP admet-9 61 26     SPACE admet-9 61 27 in in ADP admet-9 61 28     SPACE admet-9 61 29 vitro‐in vitro‐in ADJ admet-9 61 30     SPACE admet-9 61 31 vivo vivo NOUN admet-9 61 32     SPACE admet-9 61 33 correlations correlation NOUN admet-9 61 34     SPACE admet-9 61 35 and and CCONJ admet-9 61 36     SPACE admet-9 61 37 especially especially ADV admet-9 61 38     SPACE admet-9 61 39 in in ADP admet-9 61 40     SPACE admet-9 61 41 vivo vivo ADJ admet-9 61 42     SPACE admet-9 61 43 animal animal NOUN admet-9 61 44     SPACE admet-9 61 45 toxicology toxicology NOUN admet-9 61 46     SPACE admet-9 61 47 findings finding NOUN admet-9 61 48 , , PUNCT admet-9 61 49     SPACE admet-9 61 50 e.g. e.g. ADV admet-9 61 51 , , PUNCT admet-9 61 52     SPACE admet-9 61 53 abnormalities abnormality NOUN admet-9 61 54     SPACE admet-9 61 55 or or CCONJ admet-9 61 56     SPACE admet-9 61 57 even even ADV admet-9 61 58     SPACE admet-9 61 59 animal animal NOUN admet-9 61 60     SPACE admet-9 61 61 deaths death NOUN admet-9 61 62     SPACE admet-9 61 63 with with ADP admet-9 61 64     SPACE admet-9 61 65 repeat repeat NOUN admet-9 61 66     SPACE admet-9 61 67 doses dose NOUN admet-9 61 68     SPACE admet-9 61 69 on on ADP admet-9 61 70     SPACE admet-9 61 71 animal animal NOUN admet-9 61 72     SPACE admet-9 61 73 studies study NOUN admet-9 61 74 . . PUNCT admet-9 61 75     SPACE admet-9 61 76 in in ADP admet-9 61 77     SPACE admet-9 61 78 this this DET admet-9 61 79     SPACE admet-9 61 80 case case NOUN admet-9 61 81 , , PUNCT admet-9 61 82     SPACE admet-9 61 83 it it PRON admet-9 61 84     SPACE admet-9 61 85 is be AUX admet-9 61 86     SPACE admet-9 61 87 essential essential ADJ admet-9 61 88     SPACE admet-9 61 89 to to PART admet-9 61 90     SPACE admet-9 61 91 identify identify VERB admet-9 61 92     SPACE admet-9 61 93 the the DET admet-9 61 94     SPACE admet-9 61 95 biotransformed biotransformed ADJ admet-9 61 96     SPACE admet-9 61 97 metabolites metabolite NOUN admet-9 61 98     SPACE admet-9 61 99 to to PART admet-9 61 100     SPACE admet-9 61 101 understand understand VERB admet-9 61 102     SPACE admet-9 61 103 whether whether SCONJ admet-9 61 104     SPACE admet-9 61 105 the the DET admet-9 61 106     SPACE admet-9 61 107 observed observe VERB admet-9 61 108     SPACE admet-9 61 109 toxicity toxicity NOUN admet-9 61 110     SPACE admet-9 61 111 is be AUX admet-9 61 112     SPACE admet-9 61 113 due due ADJ admet-9 61 114     SPACE admet-9 61 115 to to ADP admet-9 61 116     SPACE admet-9 61 117 the the DET admet-9 61 118     SPACE admet-9 61 119 accumulation accumulation NOUN admet-9 61 120     SPACE admet-9 61 121 of of ADP admet-9 61 122     SPACE admet-9 61 123 parent parent NOUN admet-9 61 124     SPACE admet-9 61 125 exposure exposure NOUN admet-9 61 126     SPACE admet-9 61 127 or or CCONJ admet-9 61 128     SPACE admet-9 61 129 toxic toxic ADJ admet-9 61 130     SPACE admet-9 61 131 metabolites metabolite NOUN admet-9 61 132 , , PUNCT admet-9 61 133     SPACE admet-9 61 134 as as ADP admet-9 61 135     SPACE admet-9 61 136 even even ADV admet-9 61 137     SPACE admet-9 61 138 metabolites metabolite NOUN admet-9 61 139     SPACE admet-9 61 140 at at ADP admet-9 61 141     SPACE admet-9 61 142 a a DET admet-9 61 143     SPACE admet-9 61 144 level level NOUN admet-9 61 145     SPACE admet-9 61 146 lower low ADJ admet-9 61 147     SPACE admet-9 61 148 than than ADP admet-9 61 149     SPACE admet-9 61 150 10 10 NUM admet-9 61 151 % % NOUN admet-9 61 152     SPACE admet-9 61 153 admet admet NOUN admet-9 61 154     SPACE admet-9 61 155 & & CCONJ admet-9 61 156     SPACE admet-9 61 157 dmpk dmpk VERB admet-9 61 158     SPACE admet-9 61 159 1(3 1(3 NUM admet-9 61 160 ) ) PUNCT admet-9 61 161     SPACE admet-9 61 162 ( ( PUNCT admet-9 61 163 2013 2013 NUM admet-9 61 164 ) ) PUNCT admet-9 61 165     SPACE admet-9 61 166 19‐28 19‐28 NUM admet-9 61 167     SPACE admet-9 61 168 adme adme NOUN admet-9 61 169     SPACE admet-9 61 170 tests test NOUN admet-9 61 171     SPACE admet-9 61 172 for for ADP admet-9 61 173     SPACE admet-9 61 174 preclinical preclinical ADJ admet-9 61 175     SPACE admet-9 61 176 studies study NOUN admet-9 61 177     SPACE admet-9 61 178 doi doi NOUN admet-9 61 179 : : PUNCT admet-9 61 180     SPACE admet-9 61 181 10.5599 10.5599 NUM admet-9 61 182 / / SYM admet-9 61 183 admet.1.3.9 admet.1.3.9 NOUN admet-9 61 184     SPACE admet-9 61 185 23 23 NUM admet-9 61 186     SPACE admet-9 61 187 can can AUX admet-9 61 188     SPACE admet-9 61 189 accumulate accumulate VERB admet-9 61 190 . . PUNCT admet-9 61 191     SPACE admet-9 61 192 such such ADJ admet-9 61 193     SPACE admet-9 61 194 additional additional ADJ admet-9 61 195     SPACE admet-9 61 196 toxicity toxicity NOUN admet-9 61 197     SPACE admet-9 61 198 testing testing NOUN admet-9 61 199     SPACE admet-9 61 200 of of ADP admet-9 61 201     SPACE admet-9 61 202 the the DET admet-9 61 203     SPACE admet-9 61 204 major major ADJ admet-9 61 205     SPACE admet-9 61 206 metabolite metabolite NOUN admet-9 61 207     SPACE admet-9 61 208 can can AUX admet-9 61 209     SPACE admet-9 61 210 be be AUX admet-9 61 211     SPACE admet-9 61 212 informative informative ADJ admet-9 61 213     SPACE admet-9 61 214 to to PART admet-9 61 215     SPACE admet-9 61 216 confirm confirm VERB admet-9 61 217     SPACE admet-9 61 218 whether whether SCONJ admet-9 61 219     SPACE admet-9 61 220 the the DET admet-9 61 221     SPACE admet-9 61 222 cause cause NOUN admet-9 61 223     SPACE admet-9 61 224 of of ADP admet-9 61 225     SPACE admet-9 61 226 toxicity toxicity NOUN admet-9 61 227     SPACE admet-9 61 228 is be AUX admet-9 61 229     SPACE admet-9 61 230 the the DET admet-9 61 231     SPACE admet-9 61 232 metabolite metabolite NOUN admet-9 61 233     SPACE admet-9 61 234 or or CCONJ admet-9 61 235     SPACE admet-9 61 236 not not PART admet-9 61 237 . . PUNCT admet-9 61 238     SPACE admet-9 62 1 in in ADP admet-9 62 2     SPACE admet-9 62 3 this this DET admet-9 62 4     SPACE admet-9 62 5 case case NOUN admet-9 62 6 , , PUNCT admet-9 62 7     SPACE admet-9 62 8 for for ADP admet-9 62 9     SPACE admet-9 62 10 rodent rodent NOUN admet-9 62 11     SPACE admet-9 62 12 or or CCONJ admet-9 62 13     SPACE admet-9 62 14 acute acute VERB admet-9 62 15     SPACE admet-9 62 16 rat rat NOUN admet-9 62 17     SPACE admet-9 62 18 toxicology toxicology NOUN admet-9 62 19 , , PUNCT admet-9 62 20     SPACE admet-9 62 21 the the DET admet-9 62 22     SPACE admet-9 62 23 identification identification NOUN admet-9 62 24     SPACE admet-9 62 25 and and CCONJ admet-9 62 26     SPACE admet-9 62 27 profiling profiling NOUN admet-9 62 28     SPACE admet-9 62 29 of of ADP admet-9 62 30     SPACE admet-9 62 31 drug drug NOUN admet-9 62 32     SPACE admet-9 62 33 metabolites metabolite NOUN admet-9 62 34     SPACE admet-9 62 35 using use VERB admet-9 62 36     SPACE admet-9 62 37 toxicokinetic toxicokinetic ADJ admet-9 62 38     SPACE admet-9 62 39 plasma plasma NOUN admet-9 62 40     SPACE admet-9 62 41 samples sample NOUN admet-9 62 42     SPACE admet-9 62 43 can can AUX admet-9 62 44     SPACE admet-9 62 45 be be AUX admet-9 62 46     SPACE admet-9 62 47 used use VERB admet-9 62 48 . . PUNCT admet-9 62 49     SPACE admet-9 62 50 in in ADP admet-9 62 51     SPACE admet-9 62 52 short short ADJ admet-9 62 53 , , PUNCT admet-9 62 54     SPACE admet-9 62 55 relevant relevant ADJ admet-9 62 56     SPACE admet-9 62 57 studies study NOUN admet-9 62 58     SPACE admet-9 62 59 must must AUX admet-9 62 60     SPACE admet-9 62 61 be be AUX admet-9 62 62     SPACE admet-9 62 63 carried carry VERB admet-9 62 64     SPACE admet-9 62 65 out out ADP admet-9 62 66     SPACE admet-9 62 67 to to PART admet-9 62 68     SPACE admet-9 62 69 determine determine VERB admet-9 62 70     SPACE admet-9 62 71 if if SCONJ admet-9 62 72     SPACE admet-9 62 73 human human ADJ admet-9 62 74     SPACE admet-9 62 75 metabolites metabolite NOUN admet-9 62 76     SPACE admet-9 62 77 are be AUX admet-9 62 78     SPACE admet-9 62 79 adequately adequately ADV admet-9 62 80     SPACE admet-9 62 81 evaluated evaluate VERB admet-9 62 82     SPACE admet-9 62 83 during during ADP admet-9 62 84     SPACE admet-9 62 85 non‐clinical non‐clinical ADJ admet-9 62 86     SPACE admet-9 62 87 safety safety NOUN admet-9 62 88     SPACE admet-9 62 89 studies study NOUN admet-9 62 90 . . PUNCT admet-9 62 91                                                                                                                     SPACE admet-9 62 92 figure figure NOUN admet-9 62 93     SPACE admet-9 62 94 2 2 NUM admet-9 62 95 : : PUNCT admet-9 62 96     SPACE admet-9 62 97 fda fda PROPN admet-9 62 98     SPACE admet-9 62 99 suggested suggest VERB admet-9 62 100     SPACE admet-9 62 101 metabolite metabolite NOUN admet-9 62 102     SPACE admet-9 62 103 decision decision NOUN admet-9 62 104     SPACE admet-9 62 105 tree tree NOUN admet-9 62 106     SPACE admet-9 62 107 flow flow NOUN admet-9 62 108     SPACE admet-9 62 109 diagram diagram NOUN admet-9 62 110         SPACE admet-9 62 111 in in ADP admet-9 62 112     SPACE admet-9 62 113 addition addition NOUN admet-9 62 114     SPACE admet-9 62 115 to to ADP admet-9 62 116     SPACE admet-9 62 117 the the DET admet-9 62 118     SPACE admet-9 62 119 cyp cyp ADJ admet-9 62 120     SPACE admet-9 62 121 inhibition inhibition NOUN admet-9 62 122 / / SYM admet-9 62 123 induction induction NOUN admet-9 62 124     SPACE admet-9 62 125 and and CCONJ admet-9 62 126     SPACE admet-9 62 127 transporter transporter NOUN admet-9 62 128     SPACE admet-9 62 129 studies study NOUN admet-9 62 130     SPACE admet-9 62 131 associated associate VERB admet-9 62 132     SPACE admet-9 62 133 with with ADP admet-9 62 134     SPACE admet-9 62 135 ddi ddi PROPN admet-9 62 136 , , PUNCT admet-9 62 137     SPACE admet-9 62 138 other other ADJ admet-9 62 139     SPACE admet-9 62 140 safety‐related safety‐relate VERB admet-9 62 141     SPACE admet-9 62 142 studies study NOUN admet-9 62 143 , , PUNCT admet-9 62 144     SPACE admet-9 62 145 such such ADJ admet-9 62 146     SPACE admet-9 62 147 as as ADP admet-9 62 148     SPACE admet-9 62 149 reactive reactive NOUN admet-9 62 150     SPACE admet-9 62 151 metabolism metabolism NOUN admet-9 62 152     SPACE admet-9 62 153 and and CCONJ admet-9 62 154     SPACE admet-9 62 155 herg herg PROPN admet-9 62 156     SPACE admet-9 62 157 should should AUX admet-9 62 158     SPACE admet-9 62 159 be be AUX admet-9 62 160     SPACE admet-9 62 161 performed perform VERB admet-9 62 162     SPACE admet-9 62 163 as as ADP admet-9 62 164     SPACE admet-9 62 165 early early ADV admet-9 62 166     SPACE admet-9 62 167 as as ADP admet-9 62 168     SPACE admet-9 62 169 possible possible ADJ admet-9 62 170 . . PUNCT admet-9 62 171     SPACE admet-9 63 1 the the DET admet-9 63 2     SPACE admet-9 63 3 herg herg PROPN admet-9 63 4     SPACE admet-9 63 5 inhibition inhibition NOUN admet-9 63 6     SPACE admet-9 63 7 test test NOUN admet-9 63 8     SPACE admet-9 63 9 for for ADP admet-9 63 10     SPACE admet-9 63 11 cardiotoxicity cardiotoxicity NOUN admet-9 63 12     SPACE admet-9 63 13 has have AUX admet-9 63 14     SPACE admet-9 63 15 been be AUX admet-9 63 16     SPACE admet-9 63 17 shown show VERB admet-9 63 18     SPACE admet-9 63 19 to to PART admet-9 63 20     SPACE admet-9 63 21 predict predict VERB admet-9 63 22     SPACE admet-9 63 23 increased increase VERB admet-9 63 24     SPACE admet-9 63 25 risk risk NOUN admet-9 63 26     SPACE admet-9 63 27 of of ADP admet-9 63 28     SPACE admet-9 63 29 arrhythmia arrhythmia NOUN admet-9 63 30 , , PUNCT admet-9 63 31     SPACE admet-9 63 32 which which PRON admet-9 63 33     SPACE admet-9 63 34 can can AUX admet-9 63 35     SPACE admet-9 63 36 be be AUX admet-9 63 37     SPACE admet-9 63 38 initially initially ADV admet-9 63 39     SPACE admet-9 63 40 evaluated evaluate VERB admet-9 63 41     SPACE admet-9 63 42 under under ADP admet-9 63 43     SPACE admet-9 63 44 non‐glp non‐glp NOUN admet-9 63 45     SPACE admet-9 63 46 condition condition NOUN admet-9 63 47     SPACE admet-9 63 48 by by ADP admet-9 63 49     SPACE admet-9 63 50 in in ADP admet-9 63 51     SPACE admet-9 63 52 vitro vitro VERB admet-9 63 53     SPACE admet-9 63 54 approaches approach NOUN admet-9 63 55     SPACE admet-9 63 56 that that PRON admet-9 63 57     SPACE admet-9 63 58 are be AUX admet-9 63 59     SPACE admet-9 63 60 cost‐effective cost‐effective ADJ admet-9 63 61     SPACE admet-9 63 62 and and CCONJ admet-9 63 63     SPACE admet-9 63 64 have have VERB admet-9 63 65     SPACE admet-9 63 66 a a DET admet-9 63 67     SPACE admet-9 63 68 fast fast ADJ admet-9 63 69     SPACE admet-9 63 70 turnaround turnaround NOUN admet-9 63 71 , , PUNCT admet-9 63 72     SPACE admet-9 63 73 and and CCONJ admet-9 63 74     SPACE admet-9 63 75 later later ADV admet-9 63 76     SPACE admet-9 63 77 confirmed confirm VERB admet-9 63 78     SPACE admet-9 63 79 using use VERB admet-9 63 80     SPACE admet-9 63 81 qt qt NOUN admet-9 63 82     SPACE admet-9 63 83 interval interval NOUN admet-9 63 84     SPACE admet-9 63 85 prolongation prolongation NOUN admet-9 63 86     SPACE admet-9 63 87 measurements measurement NOUN admet-9 63 88     SPACE admet-9 63 89 according accord VERB admet-9 63 90     SPACE admet-9 63 91 to to ADP admet-9 63 92     SPACE admet-9 63 93 fda fda PROPN admet-9 63 94     SPACE admet-9 63 95 guidelines guideline VERB admet-9 63 96     SPACE admet-9 63 97 [ [ X admet-9 63 98 5 5 NUM admet-9 63 99 ] ] PUNCT admet-9 63 100 . . PUNCT admet-9 63 101     SPACE admet-9 64 1 another another DET admet-9 64 2     SPACE admet-9 64 3 important important ADJ admet-9 64 4     SPACE admet-9 64 5 in in ADP admet-9 64 6     SPACE admet-9 64 7 vivo vivo NOUN admet-9 64 8     SPACE admet-9 64 9 study study NOUN admet-9 64 10     SPACE admet-9 64 11 is be AUX admet-9 64 12     SPACE admet-9 64 13 basic basic ADJ admet-9 64 14     SPACE admet-9 64 15 safety safety NOUN admet-9 64 16     SPACE admet-9 64 17 tests test NOUN admet-9 64 18     SPACE admet-9 64 19 that that PRON admet-9 64 20     SPACE admet-9 64 21 are be AUX admet-9 64 22     SPACE admet-9 64 23 most most ADV admet-9 64 24     SPACE admet-9 64 25 commonly commonly ADV admet-9 64 26     SPACE admet-9 64 27 performed perform VERB admet-9 64 28     SPACE admet-9 64 29 on on ADP admet-9 64 30     SPACE admet-9 64 31 rats rat NOUN admet-9 64 32     SPACE admet-9 64 33 and and CCONJ admet-9 64 34     SPACE admet-9 64 35 dogs dog NOUN admet-9 64 36 , , PUNCT admet-9 64 37     SPACE admet-9 64 38 e.g. e.g. ADV admet-9 64 39 , , PUNCT admet-9 64 40     SPACE admet-9 64 41 non‐glp non‐glp NOUN admet-9 64 42     SPACE admet-9 64 43 acute acute NOUN admet-9 64 44     SPACE admet-9 64 45 toxicology toxicology NOUN admet-9 64 46     SPACE admet-9 64 47 ( ( PUNCT admet-9 64 48 7‐day 7‐day NOUN admet-9 64 49     SPACE admet-9 64 50 or or CCONJ admet-9 64 51     SPACE admet-9 64 52 14‐day 14‐day NOUN admet-9 64 53     SPACE admet-9 64 54 rat rat NOUN admet-9 64 55     SPACE admet-9 64 56 and and CCONJ admet-9 64 57     SPACE admet-9 64 58 dog dog NOUN admet-9 64 59     SPACE admet-9 64 60 repeat repeat NOUN admet-9 64 61     SPACE admet-9 64 62 dose dose PROPN admet-9 64 63 ) ) PUNCT admet-9 64 64     SPACE admet-9 64 65 for for ADP admet-9 64 66     SPACE admet-9 64 67 oral oral ADJ admet-9 64 68     SPACE admet-9 64 69 drugs drug NOUN admet-9 64 70 , , PUNCT admet-9 64 71     SPACE admet-9 64 72 which which PRON admet-9 64 73     SPACE admet-9 64 74 usually usually ADV admet-9 64 75     SPACE admet-9 64 76 include include VERB admet-9 64 77     SPACE admet-9 64 78 body body NOUN admet-9 64 79     SPACE admet-9 64 80 weight weight NOUN admet-9 64 81 , , PUNCT admet-9 64 82     SPACE admet-9 64 83 clinical clinical ADJ admet-9 64 84     SPACE admet-9 64 85 chemistries chemistry NOUN admet-9 64 86 , , PUNCT admet-9 64 87     SPACE admet-9 64 88 haematology haematology NOUN admet-9 64 89 , , PUNCT admet-9 64 90     SPACE admet-9 64 91 and and CCONJ admet-9 64 92     SPACE admet-9 64 93 histopathology histopathology NOUN admet-9 64 94     SPACE admet-9 64 95 ( ( PUNCT admet-9 64 96 high high ADJ admet-9 64 97     SPACE admet-9 64 98 dose dose NOUN admet-9 64 99     SPACE admet-9 64 100 and and CCONJ admet-9 64 101     SPACE admet-9 64 102 control control NOUN admet-9 64 103     SPACE admet-9 64 104 only only ADV admet-9 64 105     SPACE admet-9 64 106 if if SCONJ admet-9 64 107     SPACE admet-9 64 108 no no DET admet-9 64 109     SPACE admet-9 64 110 disproportionate disproportionate ADJ admet-9 64 111     SPACE admet-9 64 112 drug drug NOUN admet-9 64 113     SPACE admet-9 64 114 metabolite metabolite NOUN admet-9 64 115 > > PUNCT admet-9 65 1 10 10 NUM admet-9 65 2 % % NOUN admet-9 65 3     SPACE admet-9 65 4 parent parent NOUN admet-9 65 5     SPACE admet-9 65 6 systemic systemic ADJ admet-9 65 7     SPACE admet-9 65 8 exposure exposure NOUN admet-9 65 9     SPACE admet-9 65 10 � � PROPN admet-9 65 11 auc auc NOUN admet-9 65 12 � � PROPN admet-9 65 13 ≤10 ≤10 PROPN admet-9 65 14 % % NOUN admet-9 65 15     SPACE admet-9 65 16 parent parent NOUN admet-9 65 17     SPACE admet-9 65 18 systemic systemic ADJ admet-9 65 19     SPACE admet-9 65 20 exposure exposure NOUN admet-9 65 21     SPACE admet-9 65 22 � � PROPN admet-9 65 23 auc auc NOUN admet-9 65 24 � � PROPN admet-9 65 25 formed form VERB admet-9 65 26     SPACE admet-9 65 27 in in ADP admet-9 65 28     SPACE admet-9 65 29 any any DET admet-9 65 30 animal animal NOUN admet-9 65 31     SPACE admet-9 65 32 test test NOUN admet-9 65 33     SPACE admet-9 65 34 no no DET admet-9 65 35     SPACE admet-9 65 36 further far ADV admet-9 65 37     SPACE admet-9 65 38 testing testing NOUN admet-9 65 39     SPACE admet-9 65 40 needed need VERB admet-9 65 41     SPACE admet-9 65 42 yes yes INTJ admet-9 65 43 how how SCONJ admet-9 65 44     SPACE admet-9 65 45 much much ADJ admet-9 65 46 ? ? PUNCT admet-9 65 47     SPACE admet-9 66 1 no no DET admet-9 66 2 exposure exposure NOUN admet-9 66 3     SPACE admet-9 66 4 in in ADP admet-9 66 5     SPACE admet-9 66 6 animal animal NOUN admet-9 66 7 studies study NOUN admet-9 66 8     SPACE admet-9 66 9 does do AUX admet-9 66 10     SPACE admet-9 66 11 approach approach VERB admet-9 66 12     SPACE admet-9 66 13 human human ADJ admet-9 66 14     SPACE admet-9 66 15 exposure exposure NOUN admet-9 66 16     SPACE admet-9 66 17 exposure exposure NOUN admet-9 66 18     SPACE admet-9 66 19 in in ADP admet-9 66 20     SPACE admet-9 66 21 animal animal NOUN admet-9 66 22 studies study NOUN admet-9 66 23     SPACE admet-9 66 24 does do AUX admet-9 66 25     SPACE admet-9 66 26 not not PART admet-9 66 27     SPACE admet-9 66 28 approach approach NOUN admet-9 66 29     SPACE admet-9 66 30 human human ADJ admet-9 66 31     SPACE admet-9 66 32 exposure exposure NOUN admet-9 66 33     SPACE admet-9 66 34 no no DET admet-9 66 35     SPACE admet-9 66 36 further far ADV admet-9 66 37     SPACE admet-9 66 38 testing testing NOUN admet-9 66 39     SPACE admet-9 66 40 needed need VERB admet-9 66 41     SPACE admet-9 66 42 nonclinical nonclinical ADJ admet-9 66 43     SPACE admet-9 66 44 testing testing NOUN admet-9 66 45     SPACE admet-9 66 46 of of ADP admet-9 66 47 the the DET admet-9 66 48     SPACE admet-9 66 49 drug drug NOUN admet-9 66 50     SPACE admet-9 66 51 metabolite metabolite NOUN admet-9 66 52     SPACE admet-9 66 53 wan wan PROPN admet-9 66 54         SPACE admet-9 66 55 admet admet X admet-9 66 56     SPACE admet-9 66 57 & & CCONJ admet-9 66 58     SPACE admet-9 66 59 dmpk dmpk VERB admet-9 66 60     SPACE admet-9 66 61 1(3 1(3 NUM admet-9 66 62 ) ) PUNCT admet-9 66 63     SPACE admet-9 66 64 ( ( PUNCT admet-9 66 65 2013 2013 NUM admet-9 66 66 ) ) PUNCT admet-9 66 67     SPACE admet-9 66 68 19‐28 19‐28 NUM admet-9 66 69     SPACE admet-9 66 70 24 24 NUM admet-9 66 71         SPACE admet-9 66 72 pathology pathology NOUN admet-9 66 73     SPACE admet-9 66 74 is be AUX admet-9 66 75     SPACE admet-9 66 76 seen see VERB admet-9 66 77     SPACE admet-9 66 78 at at ADP admet-9 66 79     SPACE admet-9 66 80 the the DET admet-9 66 81     SPACE admet-9 66 82 high high ADJ admet-9 66 83     SPACE admet-9 66 84 dose dose NOUN admet-9 66 85 ) ) PUNCT admet-9 66 86 . . PUNCT admet-9 66 87     SPACE admet-9 67 1 this this DET admet-9 67 2     SPACE admet-9 67 3 study study NOUN admet-9 67 4     SPACE admet-9 67 5 should should AUX admet-9 67 6     SPACE admet-9 67 7 be be AUX admet-9 67 8     SPACE admet-9 67 9 designed design VERB admet-9 67 10     SPACE admet-9 67 11 to to PART admet-9 67 12     SPACE admet-9 67 13 establish establish VERB admet-9 67 14     SPACE admet-9 67 15 a a DET admet-9 67 16     SPACE admet-9 67 17 dose dose NOUN admet-9 67 18     SPACE admet-9 67 19 that that PRON admet-9 67 20     SPACE admet-9 67 21 induces induce VERB admet-9 67 22     SPACE admet-9 67 23 a a DET admet-9 67 24     SPACE admet-9 67 25 minimal minimal ADJ admet-9 67 26     SPACE admet-9 67 27 toxic toxic ADJ admet-9 67 28     SPACE admet-9 67 29 effect effect NOUN admet-9 67 30 , , PUNCT admet-9 67 31     SPACE admet-9 67 32 or or CCONJ admet-9 67 33     SPACE admet-9 67 34 alternatively alternatively ADV admet-9 67 35 , , PUNCT admet-9 67 36     SPACE admet-9 67 37 to to PART admet-9 67 38     SPACE admet-9 67 39 establish establish VERB admet-9 67 40     SPACE admet-9 67 41 a a DET admet-9 67 42     SPACE admet-9 67 43 safety safety NOUN admet-9 67 44     SPACE admet-9 67 45 margin margin NOUN admet-9 67 46     SPACE admet-9 67 47 ( ( PUNCT admet-9 67 48 e.g. e.g. ADV admet-9 67 49 , , PUNCT admet-9 67 50     SPACE admet-9 67 51 10–100x 10–100x NUM admet-9 67 52     SPACE admet-9 67 53 depending depend VERB admet-9 67 54     SPACE admet-9 67 55 on on ADP admet-9 67 56     SPACE admet-9 67 57 the the DET admet-9 67 58     SPACE admet-9 67 59 different different ADJ admet-9 67 60     SPACE admet-9 67 61 therapeutic therapeutic ADJ admet-9 67 62     SPACE admet-9 67 63 targets target NOUN admet-9 67 64 ) ) PUNCT admet-9 67 65 . . PUNCT admet-9 67 66     SPACE admet-9 68 1 the the DET admet-9 68 2     SPACE admet-9 68 3 selection selection NOUN admet-9 68 4     SPACE admet-9 68 5 of of ADP admet-9 68 6     SPACE admet-9 68 7 dose dose NOUN admet-9 68 8     SPACE admet-9 68 9 levels level NOUN admet-9 68 10     SPACE admet-9 68 11 for for ADP admet-9 68 12     SPACE admet-9 68 13 repeat repeat NOUN admet-9 68 14     SPACE admet-9 68 15 oral oral ADJ admet-9 68 16     SPACE admet-9 68 17 dose dose NOUN admet-9 68 18     SPACE admet-9 68 19 in in ADP admet-9 68 20     SPACE admet-9 68 21 toxicology toxicology NOUN admet-9 68 22     SPACE admet-9 68 23 studies study NOUN admet-9 68 24     SPACE admet-9 68 25 is be AUX admet-9 68 26     SPACE admet-9 68 27 generally generally ADV admet-9 68 28     SPACE admet-9 68 29 based base VERB admet-9 68 30     SPACE admet-9 68 31 on on ADP admet-9 68 32     SPACE admet-9 68 33 the the DET admet-9 68 34     SPACE admet-9 68 35 minimum minimum ADJ admet-9 68 36     SPACE admet-9 68 37 efficacy efficacy NOUN admet-9 68 38     SPACE admet-9 68 39 dose dose PROPN admet-9 68 40     SPACE admet-9 68 41 ( ( PUNCT admet-9 68 42 med med PROPN admet-9 68 43 ) ) PUNCT admet-9 68 44     SPACE admet-9 68 45 and and CCONJ admet-9 68 46     SPACE admet-9 68 47 the the DET admet-9 68 48     SPACE admet-9 68 49 maximum maximum NOUN admet-9 68 50     SPACE admet-9 68 51 tolerated tolerate VERB admet-9 68 52     SPACE admet-9 68 53 dose dose NOUN admet-9 68 54     SPACE admet-9 68 55 ( ( PUNCT admet-9 68 56 mtd mtd PROPN admet-9 68 57 ) ) PUNCT admet-9 68 58 . . PUNCT admet-9 68 59     SPACE admet-9 69 1 based base VERB admet-9 69 2     SPACE admet-9 69 3 on on ADP admet-9 69 4     SPACE admet-9 69 5 the the DET admet-9 69 6     SPACE admet-9 69 7 measured measure VERB admet-9 69 8     SPACE admet-9 69 9 auc auc NOUN admet-9 69 10     SPACE admet-9 69 11 ( ( PUNCT admet-9 69 12 exposures exposure NOUN admet-9 69 13 ) ) PUNCT admet-9 69 14     SPACE admet-9 69 15 and and CCONJ admet-9 69 16     SPACE admet-9 69 17 toxicokinetic toxicokinetic ADJ admet-9 69 18     SPACE admet-9 69 19 data datum NOUN admet-9 69 20 , , PUNCT admet-9 69 21     SPACE admet-9 69 22 an an DET admet-9 69 23     SPACE admet-9 69 24 approximate approximate ADJ admet-9 69 25     SPACE admet-9 69 26 safety safety NOUN admet-9 69 27     SPACE admet-9 69 28 margin margin NOUN admet-9 69 29     SPACE admet-9 69 30 and and CCONJ admet-9 69 31     SPACE admet-9 69 32 compound compound NOUN admet-9 69 33     SPACE admet-9 69 34 accumulation accumulation NOUN admet-9 69 35     SPACE admet-9 69 36 characteristics characteristic NOUN admet-9 69 37     SPACE admet-9 69 38 can can AUX admet-9 69 39     SPACE admet-9 69 40 be be AUX admet-9 69 41     SPACE admet-9 69 42 known know VERB admet-9 69 43 , , PUNCT admet-9 69 44     SPACE admet-9 69 45 which which PRON admet-9 69 46     SPACE admet-9 69 47 are be AUX admet-9 69 48     SPACE admet-9 69 49 paramount paramount ADJ admet-9 69 50     SPACE admet-9 69 51 for for ADP admet-9 69 52     SPACE admet-9 69 53 the the DET admet-9 69 54     SPACE admet-9 69 55 decision‐making decision‐making NOUN admet-9 69 56     SPACE admet-9 69 57 on on ADP admet-9 69 58     SPACE admet-9 69 59 whether whether SCONJ admet-9 69 60     SPACE admet-9 69 61 to to PART admet-9 69 62     SPACE admet-9 69 63 follow follow VERB admet-9 69 64     SPACE admet-9 69 65 up up ADP admet-9 69 66     SPACE admet-9 69 67 a a DET admet-9 69 68     SPACE admet-9 69 69 glp‐tox glp‐tox NOUN admet-9 69 70     SPACE admet-9 69 71 design design NOUN admet-9 69 72     SPACE admet-9 69 73 or or CCONJ admet-9 69 74     SPACE admet-9 69 75 not not PART admet-9 69 76 . . PUNCT admet-9 69 77     SPACE admet-9 69 78 such such ADJ admet-9 69 79     SPACE admet-9 69 80 non‐glp non‐glp NOUN admet-9 69 81     SPACE admet-9 69 82 studies study NOUN admet-9 69 83     SPACE admet-9 69 84 help help VERB admet-9 69 85     SPACE admet-9 69 86 to to PART admet-9 69 87     SPACE admet-9 69 88 identify identify VERB admet-9 69 89     SPACE admet-9 69 90 more more ADJ admet-9 69 91     SPACE admet-9 69 92 accurate accurate ADJ admet-9 69 93     SPACE admet-9 69 94 dose dose NOUN admet-9 69 95     SPACE admet-9 69 96 level level NOUN admet-9 69 97     SPACE admet-9 69 98 design design NOUN admet-9 69 99     SPACE admet-9 69 100 for for ADP admet-9 69 101     SPACE admet-9 69 102 the the DET admet-9 69 103     SPACE admet-9 69 104 subsequent subsequent ADJ admet-9 69 105     SPACE admet-9 69 106 glp glp NOUN admet-9 69 107     SPACE admet-9 69 108 studies study NOUN admet-9 69 109 . . PUNCT admet-9 69 110         SPACE admet-9 69 111 in in ADP admet-9 69 112     SPACE admet-9 69 113 summary summary NOUN admet-9 69 114 , , PUNCT admet-9 69 115     SPACE admet-9 69 116 a a DET admet-9 69 117     SPACE admet-9 69 118 comprehensive comprehensive ADJ admet-9 69 119     SPACE admet-9 69 120 nonclinical nonclinical ADJ admet-9 69 121     SPACE admet-9 69 122 adme adme PROPN admet-9 69 123 / / SYM admet-9 69 124 pk pk NOUN admet-9 69 125     SPACE admet-9 69 126 package package NOUN admet-9 69 127 , , PUNCT admet-9 69 128     SPACE admet-9 69 129 including include VERB admet-9 69 130     SPACE admet-9 69 131 key key ADJ admet-9 69 132     SPACE admet-9 69 133 toxicity toxicity NOUN admet-9 69 134     SPACE admet-9 69 135 data datum NOUN admet-9 69 136 , , PUNCT admet-9 69 137     SPACE admet-9 69 138 should should AUX admet-9 69 139     SPACE admet-9 69 140 be be AUX admet-9 69 141     SPACE admet-9 69 142 generally generally ADV admet-9 69 143     SPACE admet-9 69 144 complete complete ADJ admet-9 69 145     SPACE admet-9 69 146 by by ADP admet-9 69 147     SPACE admet-9 69 148 the the DET admet-9 69 149     SPACE admet-9 69 150 time time NOUN admet-9 69 151     SPACE admet-9 69 152 of of ADP admet-9 69 153     SPACE admet-9 69 154 cs cs PROPN admet-9 69 155 . . PROPN admet-9 69 156     SPACE admet-9 69 157 the the DET admet-9 69 158     SPACE admet-9 69 159 ultimate ultimate ADJ admet-9 69 160     SPACE admet-9 69 161 goals goal NOUN admet-9 69 162     SPACE admet-9 69 163 of of ADP admet-9 69 164     SPACE admet-9 69 165 all all DET admet-9 69 166     SPACE admet-9 69 167 adme adme NOUN admet-9 69 168 / / SYM admet-9 69 169 pk pk NOUN admet-9 69 170 / / SYM admet-9 69 171 tox tox NOUN admet-9 69 172     SPACE admet-9 69 173 studies study NOUN admet-9 69 174     SPACE admet-9 69 175 before before SCONJ admet-9 69 176     SPACE admet-9 69 177 the the DET admet-9 69 178     SPACE admet-9 69 179 cs cs ADJ admet-9 69 180     SPACE admet-9 69 181 stage stage NOUN admet-9 69 182     SPACE admet-9 69 183 are be AUX admet-9 69 184     SPACE admet-9 69 185 to to PART admet-9 69 186     SPACE admet-9 69 187 better well ADV admet-9 69 188     SPACE admet-9 69 189 understand understand VERB admet-9 69 190     SPACE admet-9 69 191 the the DET admet-9 69 192     SPACE admet-9 69 193 compound compound NOUN admet-9 69 194 ’s ’s NOUN admet-9 69 195     SPACE admet-9 69 196 metabolite‐mediated metabolite‐mediated ADJ admet-9 69 197     SPACE admet-9 69 198 toxicity toxicity NOUN admet-9 69 199     SPACE admet-9 69 200 and and CCONJ admet-9 69 201     SPACE admet-9 69 202 safety safety NOUN admet-9 69 203     SPACE admet-9 69 204 profile profile NOUN admet-9 69 205     SPACE admet-9 69 206 to to PART admet-9 69 207     SPACE admet-9 69 208 make make VERB admet-9 69 209     SPACE admet-9 69 210 a a DET admet-9 69 211     SPACE admet-9 69 212 concrete concrete ADJ admet-9 69 213     SPACE admet-9 69 214 decision decision NOUN admet-9 69 215     SPACE admet-9 69 216 for for ADP admet-9 69 217     SPACE admet-9 69 218 the the DET admet-9 69 219     SPACE admet-9 69 220 purpose purpose NOUN admet-9 69 221     SPACE admet-9 69 222 of of ADP admet-9 69 223     SPACE admet-9 69 224 enabling enable VERB admet-9 69 225     SPACE admet-9 69 226 ind ind NOUN admet-9 69 227 , , PUNCT admet-9 69 228     SPACE admet-9 69 229 which which PRON admet-9 69 230     SPACE admet-9 69 231 is be AUX admet-9 69 232     SPACE admet-9 69 233 a a DET admet-9 69 234     SPACE admet-9 69 235 crucial crucial ADJ admet-9 69 236     SPACE admet-9 69 237 part part NOUN admet-9 69 238     SPACE admet-9 69 239 of of ADP admet-9 69 240     SPACE admet-9 69 241 the the DET admet-9 69 242     SPACE admet-9 69 243 drug drug NOUN admet-9 69 244     SPACE admet-9 69 245 approval approval NOUN admet-9 69 246     SPACE admet-9 69 247 process process NOUN admet-9 69 248 . . PUNCT admet-9 69 249     SPACE admet-9 70 1 3 3 NUM admet-9 70 2 . . PUNCT admet-9 70 3     SPACE admet-9 70 4 ind‐enabling ind‐enable VERB admet-9 70 5     SPACE admet-9 70 6 package package NOUN admet-9 70 7     SPACE admet-9 70 8 for for ADP admet-9 70 9     SPACE admet-9 70 10 glp glp NOUN admet-9 70 11     SPACE admet-9 70 12 or or CCONJ admet-9 70 13     SPACE admet-9 70 14 non‐glp non‐glp NOUN admet-9 70 15 ? ? NOUN admet-9 70 16     SPACE admet-9 70 17 what what PRON admet-9 70 18     SPACE admet-9 70 19 preclinical preclinical ADJ admet-9 70 20     SPACE admet-9 70 21 studies study NOUN admet-9 70 22     SPACE admet-9 70 23 should should AUX admet-9 70 24     SPACE admet-9 70 25 be be AUX admet-9 70 26     SPACE admet-9 70 27 conducted conduct VERB admet-9 70 28     SPACE admet-9 70 29 to to PART admet-9 70 30     SPACE admet-9 70 31 enable enable VERB admet-9 70 32     SPACE admet-9 70 33 an an DET admet-9 70 34     SPACE admet-9 70 35 ind ind NOUN admet-9 70 36 ? ? PUNCT admet-9 70 37     SPACE admet-9 70 38 should should AUX admet-9 70 39     SPACE admet-9 70 40 all all DET admet-9 70 41     SPACE admet-9 70 42 studies study NOUN admet-9 70 43     SPACE admet-9 70 44 be be AUX admet-9 70 45     SPACE admet-9 70 46 performed perform VERB admet-9 70 47     SPACE admet-9 70 48 in in ADP admet-9 70 49     SPACE admet-9 70 50 glp glp NOUN admet-9 70 51     SPACE admet-9 70 52 laboratories laboratory NOUN admet-9 70 53     SPACE admet-9 70 54 for for ADP admet-9 70 55     SPACE admet-9 70 56 ind ind NOUN admet-9 70 57     SPACE admet-9 70 58 filing filing NOUN admet-9 70 59 ? ? PUNCT admet-9 70 60     SPACE admet-9 70 61 some some DET admet-9 70 62     SPACE admet-9 70 63 researchers researcher NOUN admet-9 70 64     SPACE admet-9 70 65 are be AUX admet-9 70 66     SPACE admet-9 70 67 mis‐communicating mis‐communicate VERB admet-9 70 68     SPACE admet-9 70 69 that that PRON admet-9 70 70     SPACE admet-9 70 71 at at ADP admet-9 70 72     SPACE admet-9 70 73 ind ind NOUN admet-9 70 74     SPACE admet-9 70 75 stage stage NOUN admet-9 70 76 , , PUNCT admet-9 70 77     SPACE admet-9 70 78 all all DET admet-9 70 79     SPACE admet-9 70 80 studies study NOUN admet-9 70 81     SPACE admet-9 70 82 should should AUX admet-9 70 83     SPACE admet-9 70 84 be be AUX admet-9 70 85     SPACE admet-9 70 86 conducted conduct VERB admet-9 70 87     SPACE admet-9 70 88 in in ADP admet-9 70 89     SPACE admet-9 70 90 glp glp NOUN admet-9 70 91     SPACE admet-9 70 92 laboratories laboratory NOUN admet-9 70 93 . . PUNCT admet-9 70 94     SPACE admet-9 71 1 actually actually ADV admet-9 71 2 , , PUNCT admet-9 71 3     SPACE admet-9 71 4 the the DET admet-9 71 5     SPACE admet-9 71 6 fda fda PROPN admet-9 71 7     SPACE admet-9 71 8 requires require VERB admet-9 71 9     SPACE admet-9 71 10 glp glp NOUN admet-9 71 11     SPACE admet-9 71 12 documentation documentation NOUN admet-9 71 13     SPACE admet-9 71 14 only only ADV admet-9 71 15     SPACE admet-9 71 16 for for ADP admet-9 71 17     SPACE admet-9 71 18 safety‐related safety‐relate VERB admet-9 71 19     SPACE admet-9 71 20 in in ADP admet-9 71 21     SPACE admet-9 71 22 vivo vivo NOUN admet-9 71 23     SPACE admet-9 71 24 studies study NOUN admet-9 71 25     SPACE admet-9 71 26 like like ADP admet-9 71 27     SPACE admet-9 71 28 glp‐tox glp‐tox NOUN admet-9 71 29 . . PUNCT admet-9 71 30     SPACE admet-9 71 31 in in ADP admet-9 71 32     SPACE admet-9 71 33 other other ADJ admet-9 71 34     SPACE admet-9 71 35 words word NOUN admet-9 71 36 , , PUNCT admet-9 71 37     SPACE admet-9 71 38 in in ADP admet-9 71 39     SPACE admet-9 71 40 vitro vitro VERB admet-9 71 41     SPACE admet-9 71 42 adme adme NOUN admet-9 71 43     SPACE admet-9 71 44 and and CCONJ admet-9 71 45     SPACE admet-9 71 46 in in ADP admet-9 71 47     SPACE admet-9 71 48 vivo vivo NOUN admet-9 71 49     SPACE admet-9 71 50 pk pk NOUN admet-9 71 51     SPACE admet-9 71 52 studies study NOUN admet-9 71 53     SPACE admet-9 71 54 do do AUX admet-9 71 55     SPACE admet-9 71 56 not not PART admet-9 71 57     SPACE admet-9 71 58 need need VERB admet-9 71 59     SPACE admet-9 71 60 to to PART admet-9 71 61     SPACE admet-9 71 62 be be AUX admet-9 71 63     SPACE admet-9 71 64 performed perform VERB admet-9 71 65     SPACE admet-9 71 66 in in ADP admet-9 71 67     SPACE admet-9 71 68 glp glp NOUN admet-9 71 69     SPACE admet-9 71 70 labs lab NOUN admet-9 71 71 . . PUNCT admet-9 71 72     SPACE admet-9 72 1 in in ADP admet-9 72 2     SPACE admet-9 72 3 fact fact NOUN admet-9 72 4 , , PUNCT admet-9 72 5     SPACE admet-9 72 6 from from ADP admet-9 72 7     SPACE admet-9 72 8 a a DET admet-9 72 9     SPACE admet-9 72 10 bioanalytical bioanalytical ADJ admet-9 72 11     SPACE admet-9 72 12 data data NOUN admet-9 72 13     SPACE admet-9 72 14 quality quality NOUN admet-9 72 15     SPACE admet-9 72 16 point point NOUN admet-9 72 17     SPACE admet-9 72 18 of of ADP admet-9 72 19     SPACE admet-9 72 20 view view NOUN admet-9 72 21 , , PUNCT admet-9 72 22     SPACE admet-9 72 23 there there PRON admet-9 72 24     SPACE admet-9 72 25 is be AUX admet-9 72 26     SPACE admet-9 72 27 no no DET admet-9 72 28     SPACE admet-9 72 29 apparent apparent ADJ admet-9 72 30     SPACE admet-9 72 31 discrepancy discrepancy NOUN admet-9 72 32     SPACE admet-9 72 33 between between ADP admet-9 72 34     SPACE admet-9 72 35 non‐glp non‐glp NOUN admet-9 72 36     SPACE admet-9 72 37 and and CCONJ admet-9 72 38     SPACE admet-9 72 39 glp glp NOUN admet-9 72 40     SPACE admet-9 72 41 laboratories laboratory NOUN admet-9 72 42     SPACE admet-9 72 43 regarding regard VERB admet-9 72 44     SPACE admet-9 72 45 bioanalytical bioanalytical ADJ admet-9 72 46     SPACE admet-9 72 47 procedures procedure NOUN admet-9 72 48 , , PUNCT admet-9 72 49     SPACE admet-9 72 50 because because SCONJ admet-9 72 51     SPACE admet-9 72 52 most most ADJ admet-9 72 53     SPACE admet-9 72 54 non‐glp non‐glp NOUN admet-9 72 55     SPACE admet-9 72 56 bioanalysis bioanalysis NOUN admet-9 72 57     SPACE admet-9 72 58 methods method NOUN admet-9 72 59     SPACE admet-9 72 60 are be AUX admet-9 72 61     SPACE admet-9 72 62 performed perform VERB admet-9 72 63     SPACE admet-9 72 64 according accord VERB admet-9 72 65     SPACE admet-9 72 66 to to ADP admet-9 72 67     SPACE admet-9 72 68 fda fda PROPN admet-9 72 69     SPACE admet-9 72 70 bioanalysis bioanalysis NOUN admet-9 72 71     SPACE admet-9 72 72 guidance guidance NOUN admet-9 72 73     SPACE admet-9 73 1 [ [ X admet-9 73 2 6 6 NUM admet-9 73 3 ] ] PUNCT admet-9 73 4 . . PUNCT admet-9 73 5     SPACE admet-9 74 1 the the DET admet-9 74 2     SPACE admet-9 74 3 major major ADJ admet-9 74 4     SPACE admet-9 74 5 difference difference NOUN admet-9 74 6     SPACE admet-9 74 7 can can AUX admet-9 74 8     SPACE admet-9 74 9 be be AUX admet-9 74 10     SPACE admet-9 74 11 in in ADP admet-9 74 12     SPACE admet-9 74 13 the the DET admet-9 74 14     SPACE admet-9 74 15 study study NOUN admet-9 74 16     SPACE admet-9 74 17 design design NOUN admet-9 74 18 , , PUNCT admet-9 74 19     SPACE admet-9 74 20 e.g. e.g. ADV admet-9 74 21 , , PUNCT admet-9 74 22     SPACE admet-9 74 23 a a DET admet-9 74 24     SPACE admet-9 74 25 typical typical ADJ admet-9 74 26     SPACE admet-9 74 27 non‐glp non‐glp NOUN admet-9 74 28     SPACE admet-9 74 29 tox tox NOUN admet-9 74 30     SPACE admet-9 74 31 study study NOUN admet-9 74 32     SPACE admet-9 74 33 utilises utilise VERB admet-9 74 34     SPACE admet-9 74 35 a a DET admet-9 74 36     SPACE admet-9 74 37 small small ADJ admet-9 74 38     SPACE admet-9 74 39 group group NOUN admet-9 74 40     SPACE admet-9 74 41 of of ADP admet-9 74 42     SPACE admet-9 74 43 animals animal NOUN admet-9 74 44     SPACE admet-9 74 45 ( ( PUNCT admet-9 74 46 three three NUM admet-9 74 47     SPACE admet-9 74 48 or or CCONJ admet-9 74 49     SPACE admet-9 74 50 four four NUM admet-9 74 51     SPACE admet-9 74 52 per per ADP admet-9 74 53     SPACE admet-9 74 54 group group NOUN admet-9 74 55 ) ) PUNCT admet-9 74 56 , , PUNCT admet-9 74 57     SPACE admet-9 74 58 while while SCONJ admet-9 74 59     SPACE admet-9 74 60 a a DET admet-9 74 61     SPACE admet-9 74 62 glp‐tox glp‐tox NOUN admet-9 74 63     SPACE admet-9 74 64 study study NOUN admet-9 74 65     SPACE admet-9 74 66 usually usually ADV admet-9 74 67     SPACE admet-9 74 68 utilises utilise VERB admet-9 74 69     SPACE admet-9 74 70 more more ADJ admet-9 74 71     SPACE admet-9 74 72 than than ADP admet-9 74 73     SPACE admet-9 74 74 10 10 NUM admet-9 74 75     SPACE admet-9 74 76 animals animal NOUN admet-9 74 77     SPACE admet-9 74 78 per per ADP admet-9 74 79     SPACE admet-9 74 80 group group NOUN admet-9 74 81     SPACE admet-9 74 82 with with ADP admet-9 74 83     SPACE admet-9 74 84 half half ADJ admet-9 74 85     SPACE admet-9 74 86 males male NOUN admet-9 74 87     SPACE admet-9 74 88 and and CCONJ admet-9 74 89     SPACE admet-9 74 90 half half ADJ admet-9 74 91     SPACE admet-9 74 92 females female NOUN admet-9 74 93     SPACE admet-9 74 94 in in ADP admet-9 74 95     SPACE admet-9 74 96 one one NUM admet-9 74 97     SPACE admet-9 74 98 study study NOUN admet-9 74 99 . . PUNCT admet-9 74 100     SPACE admet-9 74 101 in in ADP admet-9 74 102     SPACE admet-9 74 103 addition addition NOUN admet-9 74 104 , , PUNCT admet-9 74 105     SPACE admet-9 74 106 more more ADJ admet-9 74 107     SPACE admet-9 74 108 strict strict ADJ admet-9 74 109     SPACE admet-9 74 110 documentation documentation NOUN admet-9 74 111     SPACE admet-9 74 112 must must AUX admet-9 74 113     SPACE admet-9 74 114 be be AUX admet-9 74 115     SPACE admet-9 74 116 recorded record VERB admet-9 74 117     SPACE admet-9 74 118 for for ADP admet-9 74 119     SPACE admet-9 74 120 the the DET admet-9 74 121     SPACE admet-9 74 122 purpose purpose NOUN admet-9 74 123     SPACE admet-9 74 124 of of ADP admet-9 74 125     SPACE admet-9 74 126 regulatory regulatory ADJ admet-9 74 127     SPACE admet-9 74 128 compliance compliance NOUN admet-9 74 129 . . PUNCT admet-9 74 130     SPACE admet-9 75 1 obviously obviously ADV admet-9 75 2 , , PUNCT admet-9 75 3     SPACE admet-9 75 4 the the DET admet-9 75 5     SPACE admet-9 75 6 glp glp NOUN admet-9 75 7     SPACE admet-9 75 8 study study NOUN admet-9 75 9     SPACE admet-9 75 10 has have VERB admet-9 75 11     SPACE admet-9 75 12 much much ADJ admet-9 75 13     SPACE admet-9 75 14 higher high ADJ admet-9 75 15     SPACE admet-9 75 16 costs cost NOUN admet-9 75 17     SPACE admet-9 75 18 than than ADP admet-9 75 19     SPACE admet-9 75 20 a a DET admet-9 75 21     SPACE admet-9 75 22 similar similar ADJ admet-9 75 23     SPACE admet-9 75 24 non‐glp non‐glp NOUN admet-9 75 25     SPACE admet-9 75 26 study study NOUN admet-9 75 27 , , PUNCT admet-9 75 28     SPACE admet-9 75 29 which which PRON admet-9 75 30     SPACE admet-9 75 31 is be AUX admet-9 75 32     SPACE admet-9 75 33 not not PART admet-9 75 34     SPACE admet-9 75 35 recommended recommend VERB admet-9 75 36     SPACE admet-9 75 37 before before ADP admet-9 75 38     SPACE admet-9 75 39 cs c NOUN admet-9 75 40     SPACE admet-9 75 41 for for ADP admet-9 75 42     SPACE admet-9 75 43 the the DET admet-9 75 44     SPACE admet-9 75 45 ind‐enabling ind‐enabling ADJ admet-9 75 46     SPACE admet-9 75 47 package package NOUN admet-9 75 48 . . PUNCT admet-9 75 49     SPACE admet-9 76 1 key key ADJ admet-9 76 2     SPACE admet-9 76 3 components component NOUN admet-9 76 4     SPACE admet-9 76 5 of of ADP admet-9 76 6     SPACE admet-9 76 7 the the DET admet-9 76 8     SPACE admet-9 76 9 ind ind NOUN admet-9 76 10     SPACE admet-9 76 11 data data NOUN admet-9 76 12     SPACE admet-9 76 13 package package NOUN admet-9 76 14     SPACE admet-9 76 15 include include VERB admet-9 76 16     SPACE admet-9 76 17 pharmacology pharmacology NOUN admet-9 76 18 , , PUNCT admet-9 76 19     SPACE admet-9 76 20 toxicology toxicology NOUN admet-9 76 21     SPACE admet-9 76 22 and and CCONJ admet-9 76 23     SPACE admet-9 76 24 safety safety NOUN admet-9 76 25     SPACE admet-9 76 26 pharmacology pharmacology NOUN admet-9 76 27 , , PUNCT admet-9 76 28     SPACE admet-9 76 29 adme adme NOUN admet-9 76 30     SPACE admet-9 76 31 and and CCONJ admet-9 76 32     SPACE admet-9 76 33 chemistry chemistry NOUN admet-9 76 34 , , PUNCT admet-9 76 35     SPACE admet-9 76 36 and and CCONJ admet-9 76 37     SPACE admet-9 76 38 the the DET admet-9 76 39     SPACE admet-9 76 40 manufacturing manufacturing NOUN admet-9 76 41     SPACE admet-9 76 42 and and CCONJ admet-9 76 43     SPACE admet-9 76 44 control control NOUN admet-9 76 45     SPACE admet-9 76 46 sections section NOUN admet-9 76 47     SPACE admet-9 76 48 of of ADP admet-9 76 49     SPACE admet-9 76 50 the the DET admet-9 76 51     SPACE admet-9 76 52 submission submission NOUN admet-9 76 53 . . PUNCT admet-9 76 54     SPACE admet-9 77 1 a a DET admet-9 77 2     SPACE admet-9 77 3 typical typical ADJ admet-9 77 4     SPACE admet-9 77 5 ind‐enabling ind‐enabling NOUN admet-9 77 6     SPACE admet-9 77 7 adme adme NOUN admet-9 77 8     SPACE admet-9 77 9 package package NOUN admet-9 77 10     SPACE admet-9 77 11 contains contain VERB admet-9 77 12     SPACE admet-9 77 13 data datum NOUN admet-9 77 14     SPACE admet-9 77 15 from from ADP admet-9 77 16     SPACE admet-9 77 17 the the DET admet-9 77 18     SPACE admet-9 77 19 following follow VERB admet-9 77 20     SPACE admet-9 77 21 studies study NOUN admet-9 77 22 : : PUNCT admet-9 77 23     SPACE admet-9 77 24 bioanalytical bioanalytical ADJ admet-9 77 25     SPACE admet-9 77 26 method method NOUN admet-9 77 27     SPACE admet-9 77 28 validation validation NOUN admet-9 77 29     SPACE admet-9 77 30 in in ADP admet-9 77 31     SPACE admet-9 77 32 one one NUM admet-9 77 33     SPACE admet-9 77 34 rodent rodent NOUN admet-9 77 35     SPACE admet-9 77 36 and and CCONJ admet-9 77 37     SPACE admet-9 77 38 one one NOUN admet-9 77 39     SPACE admet-9 77 40 or or CCONJ admet-9 77 41     SPACE admet-9 77 42 more more ADJ admet-9 77 43     SPACE admet-9 77 44 non‐rodent non‐rodent ADJ admet-9 77 45     SPACE admet-9 77 46 species specie NOUN admet-9 77 47 ; ; PUNCT admet-9 77 48     SPACE admet-9 77 49 single‐ single‐ NOUN admet-9 77 50     SPACE admet-9 77 51 and and CCONJ admet-9 77 52     SPACE admet-9 77 53 multiple‐dose multiple‐dose ADJ admet-9 77 54     SPACE admet-9 77 55 pk pk NOUN admet-9 77 56 ; ; PUNCT admet-9 77 57     SPACE admet-9 77 58 dose dose NOUN admet-9 77 59     SPACE admet-9 77 60 proportionality proportionality NOUN admet-9 77 61     SPACE admet-9 77 62 and and CCONJ admet-9 77 63     SPACE admet-9 77 64 absolute absolute ADJ admet-9 77 65     SPACE admet-9 77 66 bioavailability bioavailability NOUN admet-9 77 67     SPACE admet-9 77 68 in in ADP admet-9 77 69     SPACE admet-9 77 70 one one NUM admet-9 77 71     SPACE admet-9 77 72 rodent rodent NOUN admet-9 77 73     SPACE admet-9 77 74 and and CCONJ admet-9 77 75     SPACE admet-9 77 76 one one NOUN admet-9 77 77     SPACE admet-9 77 78 or or CCONJ admet-9 77 79     SPACE admet-9 77 80 more more ADJ admet-9 77 81     SPACE admet-9 77 82 non‐rodent non‐rodent ADJ admet-9 77 83     SPACE admet-9 77 84 species specie NOUN admet-9 77 85 ; ; PUNCT admet-9 77 86     SPACE admet-9 77 87 and and CCONJ admet-9 77 88     SPACE admet-9 77 89 in in ADP admet-9 77 90     SPACE admet-9 77 91 vitro vitro VERB admet-9 77 92     SPACE admet-9 77 93 cyp cyp ADJ admet-9 77 94     SPACE admet-9 77 95 inhibition inhibition NOUN admet-9 77 96 / / SYM admet-9 77 97 induction induction NOUN admet-9 77 98     SPACE admet-9 77 99 in in ADP admet-9 77 100     SPACE admet-9 77 101 human human ADJ admet-9 77 102     SPACE admet-9 77 103 liver liver NOUN admet-9 77 104     SPACE admet-9 77 105 microsomes microsome NOUN admet-9 77 106     SPACE admet-9 77 107 for for ADP admet-9 77 108     SPACE admet-9 77 109 ddi ddi ADJ admet-9 77 110     SPACE admet-9 77 111 assessment assessment NOUN admet-9 77 112     SPACE admet-9 77 113 ( ( PUNCT admet-9 77 114 including include VERB admet-9 77 115     SPACE admet-9 77 116 likely likely ADJ admet-9 77 117     SPACE admet-9 77 118 transporter transporter NOUN admet-9 77 119     SPACE admet-9 77 120 studies study NOUN admet-9 77 121 ) ) PUNCT admet-9 77 122 . . PUNCT admet-9 77 123     SPACE admet-9 78 1 other other ADJ admet-9 78 2     SPACE admet-9 78 3 data datum NOUN admet-9 78 4 , , PUNCT admet-9 78 5     SPACE admet-9 78 6 such such ADJ admet-9 78 7     SPACE admet-9 78 8 as as ADP admet-9 78 9     SPACE admet-9 78 10 mass mass ADJ admet-9 78 11     SPACE admet-9 78 12 balance balance NOUN admet-9 78 13     SPACE admet-9 78 14 and and CCONJ admet-9 78 15     SPACE admet-9 78 16 routes route NOUN admet-9 78 17     SPACE admet-9 78 18 of of ADP admet-9 78 19     SPACE admet-9 78 20 excretion excretion NOUN admet-9 78 21     SPACE admet-9 78 22 in in ADP admet-9 78 23     SPACE admet-9 78 24 rodents rodent NOUN admet-9 78 25 , , PUNCT admet-9 78 26     SPACE admet-9 78 27 including include VERB admet-9 78 28     SPACE admet-9 78 29 bilary bilary ADJ admet-9 78 30     SPACE admet-9 78 31 excretion excretion NOUN admet-9 78 32     SPACE admet-9 78 33 in in ADP admet-9 78 34     SPACE admet-9 78 35 rats rat NOUN admet-9 78 36 , , PUNCT admet-9 78 37     SPACE admet-9 78 38 metabolite metabolite NOUN admet-9 78 39     SPACE admet-9 78 40 profiling profiling NOUN admet-9 78 41     SPACE admet-9 78 42 and and CCONJ admet-9 78 43     SPACE admet-9 78 44 identification identification NOUN admet-9 78 45     SPACE admet-9 78 46 in in ADP admet-9 78 47     SPACE admet-9 78 48 rodents rodent NOUN admet-9 78 49     SPACE admet-9 78 50 and and CCONJ admet-9 78 51     SPACE admet-9 78 52 non‐rodents non‐rodent NOUN admet-9 78 53 , , PUNCT admet-9 78 54     SPACE admet-9 78 55 tissue tissue NOUN admet-9 78 56     SPACE admet-9 78 57 distribution distribution NOUN admet-9 78 58     SPACE admet-9 78 59 using use VERB admet-9 78 60     SPACE admet-9 78 61 radio‐labelled radio‐labelled ADJ admet-9 78 62     SPACE admet-9 78 63 compound compound NOUN admet-9 78 64     SPACE admet-9 78 65 by by ADP admet-9 78 66     SPACE admet-9 78 67 quantitative quantitative ADJ admet-9 78 68     SPACE admet-9 78 69 whole‐body whole‐body ADJ admet-9 78 70     SPACE admet-9 78 71 autoradiography autoradiography NOUN admet-9 78 72     SPACE admet-9 78 73 ( ( PUNCT admet-9 78 74 qwba qwba ADJ admet-9 78 75 ) ) PUNCT admet-9 78 76     SPACE admet-9 78 77 form form NOUN admet-9 78 78     SPACE admet-9 78 79 part part NOUN admet-9 78 80     SPACE admet-9 78 81 of of ADP admet-9 78 82     SPACE admet-9 78 83 the the DET admet-9 78 84     SPACE admet-9 78 85 surrogate surrogate ADJ admet-9 78 86     SPACE admet-9 78 87 end‐points end‐point NOUN admet-9 78 88 , , PUNCT admet-9 78 89     SPACE admet-9 78 90 although although SCONJ admet-9 78 91     SPACE admet-9 78 92 these these DET admet-9 78 93     SPACE admet-9 78 94 studies study NOUN admet-9 78 95     SPACE admet-9 78 96 are be AUX admet-9 78 97     SPACE admet-9 78 98 not not PART admet-9 78 99     SPACE admet-9 78 100 required require VERB admet-9 78 101     SPACE admet-9 78 102 for for ADP admet-9 78 103     SPACE admet-9 78 104 submission submission NOUN admet-9 78 105 . . PUNCT admet-9 78 106     SPACE admet-9 79 1 overall overall ADJ admet-9 79 2 , , PUNCT admet-9 79 3     SPACE admet-9 79 4 complete complete ADJ admet-9 79 5     SPACE admet-9 79 6 adme adme NOUN admet-9 79 7     SPACE admet-9 79 8 and and CCONJ admet-9 79 9     SPACE admet-9 79 10 toxicology toxicology NOUN admet-9 79 11     SPACE admet-9 79 12 data datum NOUN admet-9 79 13     SPACE admet-9 79 14 can can AUX admet-9 79 15     SPACE admet-9 79 16 make make VERB admet-9 79 17     SPACE admet-9 79 18 the the DET admet-9 79 19     SPACE admet-9 79 20 submission submission NOUN admet-9 79 21     SPACE admet-9 79 22 package package NOUN admet-9 79 23     SPACE admet-9 79 24 more more ADJ admet-9 79 25     SPACE admet-9 79 26 compelling compelling ADJ admet-9 79 27     SPACE admet-9 79 28 to to PART admet-9 79 29     SPACE admet-9 79 30 move move VERB admet-9 79 31     SPACE admet-9 79 32 a a DET admet-9 79 33     SPACE admet-9 79 34 compound compound NOUN admet-9 79 35     SPACE admet-9 79 36 into into ADP admet-9 79 37     SPACE admet-9 79 38 phase phase NOUN admet-9 79 39     SPACE admet-9 79 40 i i PRON admet-9 79 41     SPACE admet-9 79 42 clinical clinical ADJ admet-9 79 43     SPACE admet-9 79 44 studies study NOUN admet-9 79 45 . . PUNCT admet-9 79 46     SPACE admet-9 80 1 knowing know VERB admet-9 80 2     SPACE admet-9 80 3 the the DET admet-9 80 4     SPACE admet-9 80 5 objectives objective NOUN admet-9 80 6 , , PUNCT admet-9 80 7     SPACE admet-9 80 8 expectations expectation NOUN admet-9 80 9 , , PUNCT admet-9 80 10     SPACE admet-9 80 11 and and CCONJ admet-9 80 12     SPACE admet-9 80 13 processes process NOUN admet-9 80 14     SPACE admet-9 80 15 of of ADP admet-9 80 16     SPACE admet-9 80 17 assembling assemble VERB admet-9 80 18     SPACE admet-9 80 19 and and CCONJ admet-9 80 20     SPACE admet-9 80 21 filing filing NOUN admet-9 80 22     SPACE admet-9 80 23 an an DET admet-9 80 24     SPACE admet-9 80 25 ind ind NOUN admet-9 80 26     SPACE admet-9 80 27 is be AUX admet-9 80 28     SPACE admet-9 80 29 the the DET admet-9 80 30     SPACE admet-9 80 31 key key ADJ admet-9 80 32     SPACE admet-9 80 33 factor factor NOUN admet-9 80 34     SPACE admet-9 80 35 not not PART admet-9 80 36     SPACE admet-9 80 37 only only ADV admet-9 80 38     SPACE admet-9 80 39 for for ADP admet-9 80 40     SPACE admet-9 80 41 a a DET admet-9 80 42     SPACE admet-9 80 43 successful successful ADJ admet-9 80 44     SPACE admet-9 80 45 filing filing NOUN admet-9 80 46 , , PUNCT admet-9 80 47     SPACE admet-9 80 48 but but CCONJ admet-9 80 49     SPACE admet-9 80 50 it it PRON admet-9 80 51     SPACE admet-9 80 52 can can AUX admet-9 80 53     SPACE admet-9 80 54 also also ADV admet-9 80 55     SPACE admet-9 80 56 accelerate accelerate VERB admet-9 80 57     SPACE admet-9 80 58 a a DET admet-9 80 59     SPACE admet-9 80 60 promising promising ADJ admet-9 80 61     SPACE admet-9 80 62 clinical clinical ADJ admet-9 80 63     SPACE admet-9 80 64 development development NOUN admet-9 80 65     SPACE admet-9 80 66 path path NOUN admet-9 80 67     SPACE admet-9 80 68 forward forward ADV admet-9 80 69 . . PUNCT admet-9 80 70     SPACE admet-9 81 1 more more ADJ admet-9 81 2     SPACE admet-9 81 3 detailed detailed ADJ admet-9 81 4     SPACE admet-9 81 5 information information NOUN admet-9 81 6     SPACE admet-9 81 7 on on ADP admet-9 81 8     SPACE admet-9 81 9 the the DET admet-9 81 10     SPACE admet-9 81 11 general general ADJ admet-9 81 12     SPACE admet-9 81 13 requirements requirement NOUN admet-9 81 14     SPACE admet-9 81 15 and and CCONJ admet-9 81 16     SPACE admet-9 81 17 strategies strategy NOUN admet-9 81 18     SPACE admet-9 81 19 for for ADP admet-9 81 20     SPACE admet-9 81 21 successful successful ADJ admet-9 81 22     SPACE admet-9 81 23 ind ind NOUN admet-9 81 24     SPACE admet-9 81 25 filings filing NOUN admet-9 81 26     SPACE admet-9 81 27 can can AUX admet-9 81 28     SPACE admet-9 81 29 be be AUX admet-9 81 30     SPACE admet-9 81 31 found find VERB admet-9 81 32     SPACE admet-9 81 33 in in ADP admet-9 81 34     SPACE admet-9 81 35 fda fda PROPN admet-9 81 36 ’s ’s NOUN admet-9 81 37     SPACE admet-9 81 38 guidance guidance NOUN admet-9 81 39     SPACE admet-9 82 1 [ [ X admet-9 82 2 7 7 NUM admet-9 82 3 ] ] PUNCT admet-9 82 4 , , PUNCT admet-9 82 5     SPACE admet-9 82 6 which which PRON admet-9 82 7     SPACE admet-9 82 8 is be AUX admet-9 82 9     SPACE admet-9 82 10 beyond beyond ADP admet-9 82 11     SPACE admet-9 82 12 the the DET admet-9 82 13     SPACE admet-9 82 14 scope scope NOUN admet-9 82 15     SPACE admet-9 82 16 of of ADP admet-9 82 17     SPACE admet-9 82 18 the the DET admet-9 82 19     SPACE admet-9 82 20 current current ADJ admet-9 82 21     SPACE admet-9 82 22 main main ADJ admet-9 82 23     SPACE admet-9 82 24 topic topic NOUN admet-9 82 25 . . PUNCT admet-9 82 26     SPACE admet-9 82 27 in in ADP admet-9 82 28     SPACE admet-9 82 29 order order NOUN admet-9 82 30     SPACE admet-9 82 31 to to PART admet-9 82 32     SPACE admet-9 82 33 reduce reduce VERB admet-9 82 34     SPACE admet-9 82 35 the the DET admet-9 82 36     SPACE admet-9 82 37 potential potential ADJ admet-9 82 38     SPACE admet-9 82 39 development development NOUN admet-9 82 40     SPACE admet-9 82 41 cost cost NOUN admet-9 82 42 , , PUNCT admet-9 82 43     SPACE admet-9 82 44 exploratory exploratory ADJ admet-9 82 45     SPACE admet-9 82 46 ind ind NOUN admet-9 82 47     SPACE admet-9 82 48 ( ( PUNCT admet-9 82 49 eind eind ADJ admet-9 82 50 ) ) PUNCT admet-9 82 51     SPACE admet-9 82 52 preclinical preclinical ADJ admet-9 82 53     SPACE admet-9 82 54 studies study NOUN admet-9 82 55     SPACE admet-9 82 56 are be AUX admet-9 82 57     SPACE admet-9 82 58 recommended recommend VERB admet-9 82 59     SPACE admet-9 82 60 by by ADP admet-9 82 61     SPACE admet-9 82 62 the the DET admet-9 82 63     SPACE admet-9 82 64 fda fda PROPN admet-9 82 65     SPACE admet-9 83 1 [ [ X admet-9 83 2 8 8 NUM admet-9 83 3 ] ] PUNCT admet-9 83 4 . . PUNCT admet-9 83 5     SPACE admet-9 83 6 such such ADJ admet-9 83 7     SPACE admet-9 83 8 eind eind ADJ admet-9 83 9     SPACE admet-9 83 10 studies study NOUN admet-9 83 11     SPACE admet-9 83 12 are be AUX admet-9 83 13     SPACE admet-9 83 14 conducted conduct VERB admet-9 83 15     SPACE admet-9 83 16 prior prior ADV admet-9 83 17     SPACE admet-9 83 18 to to ADP admet-9 83 19     SPACE admet-9 83 20 the the DET admet-9 83 21     SPACE admet-9 83 22 traditional traditional ADJ admet-9 83 23     SPACE admet-9 83 24 dose dose NOUN admet-9 83 25     SPACE admet-9 83 26 escalation escalation NOUN admet-9 83 27 , , PUNCT admet-9 83 28     SPACE admet-9 83 29 safety safety NOUN admet-9 83 30 , , PUNCT admet-9 83 31     SPACE admet-9 83 32 and and CCONJ admet-9 83 33     SPACE admet-9 83 34 tolerance tolerance NOUN admet-9 83 35     SPACE admet-9 83 36 studies study NOUN admet-9 83 37     SPACE admet-9 83 38 that that PRON admet-9 83 39     SPACE admet-9 83 40 ordinarily ordinarily ADV admet-9 83 41     SPACE admet-9 83 42 initiate initiate VERB admet-9 83 43     SPACE admet-9 83 44 a a DET admet-9 83 45     SPACE admet-9 83 46 clinical clinical ADJ admet-9 83 47     SPACE admet-9 83 48 development development NOUN admet-9 83 49     SPACE admet-9 83 50 program program NOUN admet-9 83 51 , , PUNCT admet-9 83 52     SPACE admet-9 83 53 which which PRON admet-9 83 54     SPACE admet-9 83 55 is be AUX admet-9 83 56     SPACE admet-9 83 57 less less ADV admet-9 83 58     SPACE admet-9 83 59 extensive extensive ADJ admet-9 83 60     SPACE admet-9 83 61 than than ADP admet-9 83 62     SPACE admet-9 83 63 for for ADP admet-9 83 64     SPACE admet-9 83 65 traditional traditional ADJ admet-9 83 66     SPACE admet-9 83 67 ind ind NOUN admet-9 83 68     SPACE admet-9 83 69 studies study NOUN admet-9 83 70 . . PUNCT admet-9 83 71     SPACE admet-9 84 1 overall overall ADV admet-9 84 2 , , PUNCT admet-9 84 3     SPACE admet-9 84 4 eind eind ADJ admet-9 84 5     SPACE admet-9 84 6 studies study NOUN admet-9 84 7     SPACE admet-9 84 8 provide provide VERB admet-9 84 9     SPACE admet-9 84 10 the the DET admet-9 84 11     SPACE admet-9 84 12 opportunity opportunity NOUN admet-9 84 13     SPACE admet-9 84 14 to to PART admet-9 84 15     SPACE admet-9 84 16 already already ADV admet-9 84 17     SPACE admet-9 84 18 obtain obtain VERB admet-9 84 19     SPACE admet-9 84 20 human human ADJ admet-9 84 21     SPACE admet-9 84 22 data datum NOUN admet-9 84 23     SPACE admet-9 84 24 in in ADP admet-9 84 25     SPACE admet-9 84 26 the the DET admet-9 84 27     SPACE admet-9 84 28 drug drug NOUN admet-9 84 29     SPACE admet-9 84 30 discovery discovery NOUN admet-9 84 31     SPACE admet-9 84 32 phase phase NOUN admet-9 84 33 , , PUNCT admet-9 84 34     SPACE admet-9 84 35 such such ADJ admet-9 84 36     SPACE admet-9 84 37 as as ADP admet-9 84 38     SPACE admet-9 84 39 important important ADJ admet-9 84 40     SPACE admet-9 84 41 information information NOUN admet-9 84 42     SPACE admet-9 84 43 on on ADP admet-9 84 44     SPACE admet-9 84 45 pk pk NOUN admet-9 84 46 , , PUNCT admet-9 84 47     SPACE admet-9 84 48 pk pk NOUN admet-9 84 49 / / SYM admet-9 84 50 pd pd PROPN admet-9 84 51 , , PUNCT admet-9 84 52     SPACE admet-9 84 53 and and CCONJ admet-9 84 54     SPACE admet-9 84 55 basic basic ADJ admet-9 84 56     SPACE admet-9 84 57 toxicology toxicology NOUN admet-9 84 58     SPACE admet-9 84 59 data datum NOUN admet-9 84 60     SPACE admet-9 84 61 for for ADP admet-9 84 62     SPACE admet-9 84 63 a a DET admet-9 84 64     SPACE admet-9 84 65 key key ADJ admet-9 84 66     SPACE admet-9 84 67 decision decision NOUN admet-9 84 68     SPACE admet-9 84 69 admet admet X admet-9 84 70     SPACE admet-9 84 71 & & CCONJ admet-9 84 72     SPACE admet-9 84 73 dmpk dmpk VERB admet-9 84 74     SPACE admet-9 84 75 1(3 1(3 NUM admet-9 84 76 ) ) PUNCT admet-9 84 77     SPACE admet-9 84 78 ( ( PUNCT admet-9 84 79 2013 2013 NUM admet-9 84 80 ) ) PUNCT admet-9 84 81     SPACE admet-9 84 82 19‐28 19‐28 NUM admet-9 84 83     SPACE admet-9 84 84 adme adme NOUN admet-9 84 85     SPACE admet-9 84 86 tests test NOUN admet-9 84 87     SPACE admet-9 84 88 for for ADP admet-9 84 89     SPACE admet-9 84 90 preclinical preclinical ADJ admet-9 84 91     SPACE admet-9 84 92 studies study NOUN admet-9 84 93     SPACE admet-9 84 94 doi doi NOUN admet-9 84 95 : : PUNCT admet-9 84 96     SPACE admet-9 84 97 10.5599 10.5599 NUM admet-9 84 98 / / SYM admet-9 84 99 admet.1.3.9 admet.1.3.9 NOUN admet-9 84 100     SPACE admet-9 84 101 25 25 NUM admet-9 84 102     SPACE admet-9 84 103 for for ADP admet-9 84 104     SPACE admet-9 84 105 selecting select VERB admet-9 84 106     SPACE admet-9 84 107 the the DET admet-9 84 108     SPACE admet-9 84 109 most most ADJ admet-9 84 110     SPACE admet-9 84 111 promising promise VERB admet-9 84 112     SPACE admet-9 84 113 lead lead ADJ admet-9 84 114     SPACE admet-9 84 115 product product NOUN admet-9 84 116 . . PUNCT admet-9 84 117     SPACE admet-9 85 1 even even ADV admet-9 85 2     SPACE admet-9 85 3 a a DET admet-9 85 4     SPACE admet-9 85 5 microdose microdose ADJ admet-9 85 6     SPACE admet-9 85 7 approach approach NOUN admet-9 85 8     SPACE admet-9 85 9 ( ( PUNCT admet-9 85 10 e.g. e.g. ADV admet-9 85 11 , , PUNCT admet-9 85 12     SPACE admet-9 85 13 < < X admet-9 85 14 100 100 NUM admet-9 85 15     SPACE admet-9 85 16 μg μg NOUN admet-9 85 17 , , PUNCT admet-9 85 18     SPACE admet-9 85 19 or or CCONJ admet-9 85 20     SPACE admet-9 85 21 < < NOUN admet-9 85 22 1/100 1/100 NUM admet-9 85 23     SPACE admet-9 85 24 of of ADP admet-9 85 25     SPACE admet-9 85 26 med med ADJ admet-9 85 27 ) ) PUNCT admet-9 85 28     SPACE admet-9 85 29 in in ADP admet-9 85 30     SPACE admet-9 85 31 a a DET admet-9 85 32     SPACE admet-9 85 33 human human ADJ admet-9 85 34     SPACE admet-9 85 35 study study NOUN admet-9 85 36 , , PUNCT admet-9 85 37     SPACE admet-9 85 38 using use VERB admet-9 85 39     SPACE admet-9 85 40 an an DET admet-9 85 41     SPACE admet-9 85 42 advanced advanced ADJ admet-9 85 43     SPACE admet-9 85 44 technology technology NOUN admet-9 85 45     SPACE admet-9 85 46 such such ADJ admet-9 85 47     SPACE admet-9 85 48 as as ADP admet-9 85 49     SPACE admet-9 85 50 accelerator accelerator NOUN admet-9 85 51     SPACE admet-9 85 52 mass mass PROPN admet-9 85 53     SPACE admet-9 85 54 spectrometry spectrometry NOUN admet-9 85 55     SPACE admet-9 85 56 ( ( PUNCT admet-9 85 57 ams am NOUN admet-9 85 58 ) ) PUNCT admet-9 85 59     SPACE admet-9 85 60 combined combine VERB admet-9 85 61     SPACE admet-9 85 62 with with ADP admet-9 85 63     SPACE admet-9 85 64 radio‐labelled radio‐labelled ADJ admet-9 85 65     SPACE admet-9 85 66 compound compound NOUN admet-9 85 67     SPACE admet-9 85 68 can can AUX admet-9 85 69     SPACE admet-9 85 70 be be AUX admet-9 85 71     SPACE admet-9 85 72 very very ADV admet-9 85 73     SPACE admet-9 85 74 beneficial beneficial ADJ admet-9 85 75     SPACE admet-9 85 76 to to PART admet-9 85 77     SPACE admet-9 85 78 gain gain VERB admet-9 85 79     SPACE admet-9 85 80 human human ADJ admet-9 85 81     SPACE admet-9 85 82 pk pk NOUN admet-9 85 83     SPACE admet-9 85 84 information information NOUN admet-9 85 85     SPACE admet-9 85 86 as as ADP admet-9 85 87     SPACE admet-9 85 88 early early ADV admet-9 85 89     SPACE admet-9 85 90 as as ADP admet-9 85 91     SPACE admet-9 85 92 possible possible ADJ admet-9 85 93     SPACE admet-9 85 94 for for ADP admet-9 85 95     SPACE admet-9 85 96 ind ind NOUN admet-9 85 97     SPACE admet-9 85 98 enabling enable VERB admet-9 85 99     SPACE admet-9 86 1 [ [ X admet-9 86 2 9 9 NUM admet-9 86 3 ] ] PUNCT admet-9 86 4 . . PUNCT admet-9 86 5     SPACE admet-9 87 1 4 4 NUM admet-9 87 2 . . PUNCT admet-9 87 3     SPACE admet-9 87 4 what what PRON admet-9 87 5     SPACE admet-9 87 6 is be AUX admet-9 87 7     SPACE admet-9 87 8 a a DET admet-9 87 9     SPACE admet-9 87 10 good good ADJ admet-9 87 11     SPACE admet-9 87 12 pk pk NOUN admet-9 87 13     SPACE admet-9 87 14 profile profile NOUN admet-9 87 15 ? ? PUNCT admet-9 87 16     SPACE admet-9 87 17 another another DET admet-9 87 18     SPACE admet-9 87 19 frequent frequent ADJ admet-9 87 20     SPACE admet-9 87 21 question question NOUN admet-9 87 22     SPACE admet-9 87 23 asked ask VERB admet-9 87 24     SPACE admet-9 87 25 by by ADP admet-9 87 26     SPACE admet-9 87 27 drug drug NOUN admet-9 87 28     SPACE admet-9 87 29 discovery discovery NOUN admet-9 87 30     SPACE admet-9 87 31 scientists scientist NOUN admet-9 87 32     SPACE admet-9 87 33 is be AUX admet-9 87 34     SPACE admet-9 87 35 ‘ ' PUNCT admet-9 87 36 is be AUX admet-9 87 37     SPACE admet-9 87 38 this this DET admet-9 87 39     SPACE admet-9 87 40 compound compound NOUN admet-9 87 41 ’s ’s NOUN admet-9 87 42     SPACE admet-9 87 43 pk pk NOUN admet-9 87 44     SPACE admet-9 87 45 good good ADJ admet-9 87 46 ? ? PUNCT admet-9 87 47 ’ ' PUNCT admet-9 87 48     SPACE admet-9 87 49 ideally ideally ADV admet-9 87 50 , , PUNCT admet-9 87 51     SPACE admet-9 87 52 the the DET admet-9 87 53     SPACE admet-9 87 54 desirable desirable ADJ admet-9 87 55     SPACE admet-9 87 56 pk pk NOUN admet-9 87 57     SPACE admet-9 87 58 profiles profile NOUN admet-9 87 59     SPACE admet-9 87 60 of of ADP admet-9 87 61     SPACE admet-9 87 62 a a DET admet-9 87 63     SPACE admet-9 87 64 preclinical preclinical ADJ admet-9 87 65     SPACE admet-9 87 66 candidate candidate NOUN admet-9 87 67     SPACE admet-9 87 68 that that PRON admet-9 87 69     SPACE admet-9 87 70 is be AUX admet-9 87 71     SPACE admet-9 87 72 being be AUX admet-9 87 73     SPACE admet-9 87 74 considered consider VERB admet-9 87 75     SPACE admet-9 87 76 for for ADP admet-9 87 77     SPACE admet-9 87 78 taking taking NOUN admet-9 87 79     SPACE admet-9 87 80 into into ADP admet-9 87 81     SPACE admet-9 87 82 development development NOUN admet-9 87 83     SPACE admet-9 87 84 should should AUX admet-9 87 85 : : PUNCT admet-9 87 86     SPACE admet-9 87 87 • • NOUN admet-9 87 88 have have VERB admet-9 87 89     SPACE admet-9 87 90 acceptable acceptable ADJ admet-9 87 91     SPACE admet-9 87 92 solubility solubility NOUN admet-9 87 93     SPACE admet-9 87 94 for for ADP admet-9 87 95     SPACE admet-9 87 96 development development NOUN admet-9 87 97 ; ; PUNCT admet-9 87 98     SPACE admet-9 87 99 • • NUM admet-9 87 100 be be AUX admet-9 87 101     SPACE admet-9 87 102 completely completely ADV admet-9 87 103     SPACE admet-9 87 104 absorbed absorb VERB admet-9 87 105 , , PUNCT admet-9 87 106     SPACE admet-9 87 107 preferably preferably ADV admet-9 87 108     SPACE admet-9 87 109 via via ADP admet-9 87 110     SPACE admet-9 87 111 passive passive ADJ admet-9 87 112     SPACE admet-9 87 113 absorption absorption NOUN admet-9 87 114 ; ; PUNCT admet-9 87 115     SPACE admet-9 87 116 • • NOUN admet-9 87 117 have have VERB admet-9 87 118     SPACE admet-9 87 119 high high ADJ admet-9 87 120     SPACE admet-9 87 121 bioavailability bioavailability NOUN admet-9 87 122     SPACE admet-9 87 123 ( ( PUNCT admet-9 87 124 e.g. e.g. ADV admet-9 87 125 , , PUNCT admet-9 87 126     SPACE admet-9 87 127 f>50 f>50 NUM admet-9 87 128 % % NOUN admet-9 87 129 ) ) PUNCT admet-9 87 130     SPACE admet-9 87 131 for for ADP admet-9 87 132     SPACE admet-9 87 133 oral oral ADJ admet-9 87 134     SPACE admet-9 87 135 drug drug NOUN admet-9 87 136 ; ; PUNCT admet-9 87 137     SPACE admet-9 87 138 • • NOUN admet-9 87 139 have have VERB admet-9 87 140     SPACE admet-9 87 141 a a DET admet-9 87 142     SPACE admet-9 87 143 low low ADJ admet-9 87 144     SPACE admet-9 87 145 plasma plasma NOUN admet-9 87 146     SPACE admet-9 87 147 clearance clearance NOUN admet-9 87 148     SPACE admet-9 87 149 cl cl NOUN admet-9 87 150     SPACE admet-9 87 151 ( ( PUNCT admet-9 87 152 e.g e.g PROPN admet-9 87 153 , , PUNCT admet-9 87 154     SPACE admet-9 87 155 < < X admet-9 87 156 30 30 NUM admet-9 87 157 % % NOUN admet-9 87 158     SPACE admet-9 87 159 blood blood NOUN admet-9 87 160     SPACE admet-9 87 161 flow flow NOUN admet-9 87 162 ) ) PUNCT admet-9 87 163 , , PUNCT admet-9 87 164     SPACE admet-9 87 165 long long ADJ admet-9 87 166     SPACE admet-9 87 167 half‐life half‐life NOUN admet-9 87 168     SPACE admet-9 87 169 ( ( PUNCT admet-9 87 170 t1/2 t1/2 PROPN admet-9 87 171 ) ) PUNCT admet-9 87 172     SPACE admet-9 87 173 ( ( PUNCT admet-9 87 174 e.g. e.g. ADV admet-9 87 175 , , PUNCT admet-9 87 176     SPACE admet-9 87 177 > > X admet-9 87 178 6 6 NUM admet-9 87 179     SPACE admet-9 87 180 hrs hrs NOUN admet-9 87 181 ) ) PUNCT admet-9 87 182 , , PUNCT admet-9 87 183     SPACE admet-9 87 184 and and CCONJ admet-9 87 185     SPACE admet-9 87 186 acceptable acceptable ADJ admet-9 87 187     SPACE admet-9 87 188 distribution distribution NOUN admet-9 87 189     SPACE admet-9 87 190 volume volume NOUN admet-9 87 191 ; ; PUNCT admet-9 87 192     SPACE admet-9 87 193 • • NOUN admet-9 87 194 have have VERB admet-9 87 195     SPACE admet-9 87 196 a a DET admet-9 87 197     SPACE admet-9 87 198 linear linear NOUN admet-9 87 199     SPACE admet-9 87 200 kinetics kinetic NOUN admet-9 87 201 , , PUNCT admet-9 87 202     SPACE admet-9 87 203 i.e. i.e. X admet-9 87 204 , , PUNCT admet-9 87 205     SPACE admet-9 87 206 exposure exposure NOUN admet-9 87 207     SPACE admet-9 87 208 proportional proportional NOUN admet-9 87 209     SPACE admet-9 87 210 to to PART admet-9 87 211     SPACE admet-9 87 212 dose dose VERB admet-9 87 213     SPACE admet-9 87 214 and and CCONJ admet-9 87 215     SPACE admet-9 87 216 a a DET admet-9 87 217     SPACE admet-9 87 218 clear clear ADJ admet-9 87 219     SPACE admet-9 87 220 pk pk NOUN admet-9 87 221 / / SYM admet-9 87 222 pd pd NOUN admet-9 87 223     SPACE admet-9 87 224 correlation correlation NOUN admet-9 87 225 ; ; PUNCT admet-9 87 226     SPACE admet-9 87 227 • • NUM admet-9 87 228 be be AUX admet-9 87 229     SPACE admet-9 87 230 eliminated eliminate VERB admet-9 87 231     SPACE admet-9 87 232 by by ADP admet-9 87 233     SPACE admet-9 87 234 several several ADJ admet-9 87 235     SPACE admet-9 87 236 pathways pathway NOUN admet-9 87 237 , , PUNCT admet-9 87 238     SPACE admet-9 87 239 i.e. i.e. X admet-9 87 240 , , PUNCT admet-9 87 241     SPACE admet-9 87 242 renal renal ADJ admet-9 87 243     SPACE admet-9 87 244 excretion excretion NOUN admet-9 87 245     SPACE admet-9 87 246 and and CCONJ admet-9 87 247     SPACE admet-9 87 248 hepatic hepatic ADJ admet-9 87 249     SPACE admet-9 87 250 metabolism metabolism NOUN admet-9 87 251 , , PUNCT admet-9 87 252     SPACE admet-9 87 253 also also ADV admet-9 87 254     SPACE admet-9 87 255 metabolised metabolise VERB admet-9 87 256     SPACE admet-9 87 257 preferably preferably ADV admet-9 87 258     SPACE admet-9 87 259 by by ADP admet-9 87 260     SPACE admet-9 87 261 more more ADJ admet-9 87 262     SPACE admet-9 87 263 than than ADP admet-9 87 264     SPACE admet-9 87 265 one one NUM admet-9 87 266     SPACE admet-9 87 267 enzyme enzyme NOUN admet-9 87 268     SPACE admet-9 87 269 for for ADP admet-9 87 270     SPACE admet-9 87 271 de‐risking de‐riske VERB admet-9 87 272     SPACE admet-9 87 273 ddi ddi PROPN admet-9 87 274 ; ; PUNCT admet-9 87 275     SPACE admet-9 87 276 • • NOUN admet-9 87 277 have have VERB admet-9 87 278     SPACE admet-9 87 279 a a DET admet-9 87 280     SPACE admet-9 87 281 simple simple ADJ admet-9 87 282     SPACE admet-9 87 283 metabolite metabolite NOUN admet-9 87 284     SPACE admet-9 87 285 profile profile NOUN admet-9 87 286 , , PUNCT admet-9 87 287     SPACE admet-9 87 288 with with ADP admet-9 87 289     SPACE admet-9 87 290 no no DET admet-9 87 291     SPACE admet-9 87 292 reactive reactive NOUN admet-9 87 293     SPACE admet-9 87 294 metabolite metabolite NOUN admet-9 87 295 ; ; PUNCT admet-9 87 296     SPACE admet-9 87 297 • • NOUN admet-9 87 298 have have VERB admet-9 87 299     SPACE admet-9 87 300 no no PRON admet-9 87 301     SPACE admet-9 87 302 obvious obvious ADJ admet-9 87 303     SPACE admet-9 87 304 cyp cyp ADJ admet-9 87 305     SPACE admet-9 87 306 and and CCONJ admet-9 87 307     SPACE admet-9 87 308 major major ADJ admet-9 87 309     SPACE admet-9 87 310 transporters transporter NOUN admet-9 87 311     SPACE admet-9 87 312 like like ADP admet-9 87 313     SPACE admet-9 87 314 p‐gp p‐gp NOUN admet-9 87 315     SPACE admet-9 87 316 inhibition inhibition NOUN admet-9 87 317     SPACE admet-9 87 318 or or CCONJ admet-9 87 319     SPACE admet-9 87 320 induction induction NOUN admet-9 87 321     SPACE admet-9 87 322 or or CCONJ admet-9 87 323     SPACE admet-9 87 324 low low ADJ admet-9 87 325     SPACE admet-9 87 326 ddi ddi ADJ admet-9 87 327     SPACE admet-9 87 328 potential potential NOUN admet-9 87 329 ; ; PUNCT admet-9 87 330     SPACE admet-9 87 331 and and CCONJ admet-9 87 332     SPACE admet-9 87 333 • • NOUN admet-9 87 334 have have VERB admet-9 87 335     SPACE admet-9 87 336 a a DET admet-9 87 337     SPACE admet-9 87 338 sufficient sufficient ADJ admet-9 87 339     SPACE admet-9 87 340 or or CCONJ admet-9 87 341     SPACE admet-9 87 342 at at ADP admet-9 87 343     SPACE admet-9 87 344 least least ADJ admet-9 87 345     SPACE admet-9 87 346 acceptable acceptable ADJ admet-9 87 347     SPACE admet-9 87 348 safety safety NOUN admet-9 87 349     SPACE admet-9 87 350 margin margin NOUN admet-9 87 351     SPACE admet-9 87 352 ( ( PUNCT admet-9 87 353 safety safety NOUN admet-9 87 354     SPACE admet-9 87 355 margin margin NOUN admet-9 87 356     SPACE admet-9 87 357 > > X admet-9 87 358 10x 10x NOUN admet-9 87 359 , , PUNCT admet-9 87 360     SPACE admet-9 87 361 depending depend VERB admet-9 87 362     SPACE admet-9 87 363 on on ADP admet-9 87 364     SPACE admet-9 87 365 different different ADJ admet-9 87 366     SPACE admet-9 87 367 therapeutic therapeutic ADJ admet-9 87 368     SPACE admet-9 87 369 targets target NOUN admet-9 87 370 ) ) PUNCT admet-9 87 371 . . PUNCT admet-9 87 372         SPACE admet-9 87 373 in in ADP admet-9 87 374     SPACE admet-9 87 375 reality reality NOUN admet-9 87 376 , , PUNCT admet-9 87 377     SPACE admet-9 87 378 we we PRON admet-9 87 379     SPACE admet-9 87 380 can can AUX admet-9 87 381     SPACE admet-9 87 382 readily readily ADV admet-9 87 383     SPACE admet-9 87 384 rank rank NOUN admet-9 87 385     SPACE admet-9 87 386 which which DET admet-9 87 387     SPACE admet-9 87 388 compound compound VERB admet-9 87 389 ’s ’s NOUN admet-9 87 390     SPACE admet-9 87 391 pk pk NOUN admet-9 87 392     SPACE admet-9 87 393 is be AUX admet-9 87 394     SPACE admet-9 87 395 better well ADJ admet-9 87 396     SPACE admet-9 87 397 than than ADP admet-9 87 398     SPACE admet-9 87 399 others other NOUN admet-9 87 400     SPACE admet-9 87 401 from from ADP admet-9 87 402     SPACE admet-9 87 403 the the DET admet-9 87 404     SPACE admet-9 87 405 same same ADJ admet-9 87 406     SPACE admet-9 87 407 series series NOUN admet-9 87 408     SPACE admet-9 87 409 of of ADP admet-9 87 410     SPACE admet-9 87 411 compounds compound NOUN admet-9 87 412     SPACE admet-9 87 413 during during ADP admet-9 87 414     SPACE admet-9 87 415 the the DET admet-9 87 416     SPACE admet-9 87 417 screening screening NOUN admet-9 87 418 . . PUNCT admet-9 87 419     SPACE admet-9 88 1 however however ADV admet-9 88 2 , , PUNCT admet-9 88 3     SPACE admet-9 88 4 we we PRON admet-9 88 5     SPACE admet-9 88 6 should should AUX admet-9 88 7     SPACE admet-9 88 8 not not PART admet-9 88 9     SPACE admet-9 88 10 rule rule VERB admet-9 88 11     SPACE admet-9 88 12 out out ADP admet-9 88 13     SPACE admet-9 88 14 a a DET admet-9 88 15     SPACE admet-9 88 16 compound compound NOUN admet-9 88 17     SPACE admet-9 88 18 by by ADP admet-9 88 19     SPACE admet-9 88 20 only only ADV admet-9 88 21     SPACE admet-9 88 22 looking look VERB admet-9 88 23     SPACE admet-9 88 24 at at ADP admet-9 88 25     SPACE admet-9 88 26 its its PRON admet-9 88 27     SPACE admet-9 88 28 pk pk NOUN admet-9 88 29     SPACE admet-9 88 30 data datum NOUN admet-9 88 31 , , PUNCT admet-9 88 32     SPACE admet-9 88 33 especially especially ADV admet-9 88 34     SPACE admet-9 88 35 for for ADP admet-9 88 36     SPACE admet-9 88 37 those those PRON admet-9 88 38     SPACE admet-9 88 39 with with ADP admet-9 88 40     SPACE admet-9 88 41 super super ADJ admet-9 88 42     SPACE admet-9 88 43 potent potent NOUN admet-9 88 44     SPACE admet-9 88 45 nmes nme NOUN admet-9 88 46 . . PUNCT admet-9 88 47     SPACE admet-9 89 1 as as ADV admet-9 89 2     SPACE admet-9 89 3 long long ADV admet-9 89 4     SPACE admet-9 89 5 as as ADP admet-9 89 6     SPACE admet-9 89 7 their their PRON admet-9 89 8     SPACE admet-9 89 9 potencies potency NOUN admet-9 89 10     SPACE admet-9 89 11 and and CCONJ admet-9 89 12     SPACE admet-9 89 13 mechanism mechanism NOUN admet-9 89 14     SPACE admet-9 89 15 are be AUX admet-9 89 16     SPACE admet-9 89 17 attractive attractive ADJ admet-9 89 18 , , PUNCT admet-9 89 19     SPACE admet-9 89 20 they they PRON admet-9 89 21     SPACE admet-9 89 22 should should AUX admet-9 89 23     SPACE admet-9 89 24 be be AUX admet-9 89 25     SPACE admet-9 89 26 tested test VERB admet-9 89 27     SPACE admet-9 89 28 in in ADP admet-9 89 29     SPACE admet-9 89 30 in in ADP admet-9 89 31     SPACE admet-9 89 32 vivo vivo NOUN admet-9 89 33     SPACE admet-9 89 34 efficacy efficacy NOUN admet-9 89 35     SPACE admet-9 89 36 models model NOUN admet-9 89 37     SPACE admet-9 89 38 despite despite SCONJ admet-9 89 39     SPACE admet-9 89 40 poor poor ADJ admet-9 89 41     SPACE admet-9 89 42 pk pk NOUN admet-9 89 43     SPACE admet-9 89 44 profiles profile NOUN admet-9 89 45 . . PUNCT admet-9 89 46     SPACE admet-9 89 47 indeed indeed ADV admet-9 89 48 , , PUNCT admet-9 89 49     SPACE admet-9 89 50 a a DET admet-9 89 51     SPACE admet-9 89 52 number number NOUN admet-9 89 53     SPACE admet-9 89 54 of of ADP admet-9 89 55     SPACE admet-9 89 56 marketed market VERB admet-9 89 57     SPACE admet-9 89 58 drugs drug NOUN admet-9 89 59     SPACE admet-9 89 60 have have AUX admet-9 89 61     SPACE admet-9 89 62 shown show VERB admet-9 89 63     SPACE admet-9 89 64 poor poor ADJ admet-9 89 65     SPACE admet-9 89 66 pk pk NOUN admet-9 89 67     SPACE admet-9 89 68 profiles profile NOUN admet-9 89 69     SPACE admet-9 89 70 but but CCONJ admet-9 89 71     SPACE admet-9 89 72 have have AUX admet-9 89 73     SPACE admet-9 89 74 still still ADV admet-9 89 75     SPACE admet-9 89 76 become become VERB admet-9 89 77     SPACE admet-9 89 78 the the DET admet-9 89 79     SPACE admet-9 89 80 top top NOUN admet-9 89 81     SPACE admet-9 89 82 ever ever ADV admet-9 89 83     SPACE admet-9 89 84 selling sell VERB admet-9 89 85     SPACE admet-9 89 86 drug drug NOUN admet-9 89 87     SPACE admet-9 89 88 – – PUNCT admet-9 89 89     SPACE admet-9 89 90 lipitor lipitor NOUN admet-9 89 91     SPACE admet-9 89 92 ( ( PUNCT admet-9 89 93 atorvastatin atorvastatin PROPN admet-9 89 94 ) ) PUNCT admet-9 89 95 , , PUNCT admet-9 89 96     SPACE admet-9 89 97 with with ADP admet-9 89 98     SPACE admet-9 89 99 absolute absolute ADJ admet-9 89 100     SPACE admet-9 89 101 bioavailability bioavailability NOUN admet-9 89 102     SPACE admet-9 89 103 of of ADP admet-9 89 104     SPACE admet-9 89 105 5 5 NUM admet-9 89 106 % % NOUN admet-9 89 107     SPACE admet-9 89 108 and and CCONJ admet-9 89 109     SPACE admet-9 89 110 14 14 NUM admet-9 89 111 % % NOUN admet-9 89 112     SPACE admet-9 89 113 in in ADP admet-9 89 114     SPACE admet-9 89 115 rat rat NOUN admet-9 89 116     SPACE admet-9 89 117 and and CCONJ admet-9 89 118     SPACE admet-9 89 119 human human NOUN admet-9 89 120 , , PUNCT admet-9 89 121     SPACE admet-9 89 122 respectively respectively ADV admet-9 89 123     SPACE admet-9 90 1 [ [ X admet-9 90 2 10,11 10,11 NOUN admet-9 90 3 ] ] X admet-9 90 4 . . PUNCT admet-9 90 5     SPACE admet-9 91 1 as as SCONJ admet-9 91 2     SPACE admet-9 91 3 illustrated illustrate VERB admet-9 91 4     SPACE admet-9 91 5 in in ADP admet-9 91 6     SPACE admet-9 91 7 figure figure NOUN admet-9 91 8     SPACE admet-9 91 9 3 3 NUM admet-9 91 10 , , PUNCT admet-9 91 11     SPACE admet-9 91 12 in in ADP admet-9 91 13     SPACE admet-9 91 14 an an DET admet-9 91 15     SPACE admet-9 91 16 analysis analysis NOUN admet-9 91 17     SPACE admet-9 91 18 of of ADP admet-9 91 19     SPACE admet-9 91 20 600 600 NUM admet-9 91 21     SPACE admet-9 91 22 market market NOUN admet-9 91 23     SPACE admet-9 91 24 drugs drug NOUN admet-9 91 25     SPACE admet-9 92 1 [ [ X admet-9 92 2 12 12 NUM admet-9 92 3 ] ] PUNCT admet-9 92 4 , , PUNCT admet-9 92 5     SPACE admet-9 92 6 more more ADJ admet-9 92 7     SPACE admet-9 92 8 than than ADP admet-9 92 9     SPACE admet-9 92 10 30 30 NUM admet-9 92 11 % % NOUN admet-9 92 12     SPACE admet-9 92 13 of of ADP admet-9 92 14     SPACE admet-9 92 15 them they PRON admet-9 92 16     SPACE admet-9 92 17 have have AUX admet-9 92 18     SPACE admet-9 92 19 relatively relatively ADV admet-9 92 20     SPACE admet-9 92 21 low low ADJ admet-9 92 22     SPACE admet-9 92 23 bioavailability bioavailability NOUN admet-9 92 24     SPACE admet-9 92 25 ( ( PUNCT admet-9 92 26 f f X admet-9 92 27     SPACE admet-9 92 28 < < X admet-9 92 29 30 30 NUM admet-9 92 30 % % NOUN admet-9 92 31 ) ) PUNCT admet-9 92 32 , , PUNCT admet-9 92 33     SPACE admet-9 92 34 and and CCONJ admet-9 92 35     SPACE admet-9 92 36 22 22 NUM admet-9 92 37 % % NOUN admet-9 92 38     SPACE admet-9 92 39 of of ADP admet-9 92 40     SPACE admet-9 92 41 the the DET admet-9 92 42     SPACE admet-9 92 43 drugs drug NOUN admet-9 92 44     SPACE admet-9 92 45 have have VERB admet-9 92 46     SPACE admet-9 92 47 even even ADV admet-9 92 48     SPACE admet-9 92 49 lower low ADJ admet-9 92 50     SPACE admet-9 92 51 bioavailability bioavailability NOUN admet-9 92 52     SPACE admet-9 92 53 ( ( PUNCT admet-9 92 54 f f NOUN admet-9 92 55     SPACE admet-9 92 56 < < X admet-9 92 57 10 10 NUM admet-9 92 58     SPACE admet-9 92 59 % % NOUN admet-9 92 60 ) ) PUNCT admet-9 92 61 . . PUNCT admet-9 92 62     SPACE admet-9 93 1 nearly nearly ADV admet-9 93 2     SPACE admet-9 93 3 50 50 NUM admet-9 93 4 % % NOUN admet-9 93 5     SPACE admet-9 93 6 of of ADP admet-9 93 7     SPACE admet-9 93 8 the the DET admet-9 93 9     SPACE admet-9 93 10 drugs drug NOUN admet-9 93 11     SPACE admet-9 93 12 have have VERB admet-9 93 13     SPACE admet-9 93 14 moderate‐to‐high moderate‐to‐high PROPN admet-9 93 15     SPACE admet-9 93 16 clearance clearance NOUN admet-9 93 17 , , PUNCT admet-9 93 18     SPACE admet-9 93 19 and and CCONJ admet-9 93 20     SPACE admet-9 93 21 17 17 NUM admet-9 93 22 % % NOUN admet-9 93 23     SPACE admet-9 93 24 show show NOUN admet-9 93 25     SPACE admet-9 93 26 high high ADJ admet-9 93 27     SPACE admet-9 93 28 clearance clearance NOUN admet-9 93 29 , , PUNCT admet-9 93 30     SPACE admet-9 93 31 or or CCONJ admet-9 93 32     SPACE admet-9 93 33 extremely extremely ADV admet-9 93 34     SPACE admet-9 93 35 high high ADJ admet-9 93 36     SPACE admet-9 93 37 clearance clearance NOUN admet-9 93 38     SPACE admet-9 93 39 ( ( PUNCT admet-9 93 40 even even ADV admet-9 93 41     SPACE admet-9 93 42 over over ADP admet-9 93 43     SPACE admet-9 93 44 blood blood NOUN admet-9 93 45     SPACE admet-9 93 46 flow flow NOUN admet-9 93 47 ) ) PUNCT admet-9 93 48 . . PUNCT admet-9 93 49     SPACE admet-9 94 1 as as SCONJ admet-9 94 2     SPACE admet-9 94 3 mentioned mention VERB admet-9 94 4     SPACE admet-9 94 5 above above ADV admet-9 94 6 , , PUNCT admet-9 94 7     SPACE admet-9 94 8 some some PRON admet-9 94 9     SPACE admet-9 94 10 of of ADP admet-9 94 11     SPACE admet-9 94 12 these these DET admet-9 94 13     SPACE admet-9 94 14 top top ADJ admet-9 94 15     SPACE admet-9 94 16 selling selling NOUN admet-9 94 17     SPACE admet-9 94 18 drugs drug NOUN admet-9 94 19     SPACE admet-9 94 20 have have VERB admet-9 94 21     SPACE admet-9 94 22 many many ADJ admet-9 94 23     SPACE admet-9 94 24 undesirable undesirable ADJ admet-9 94 25     SPACE admet-9 94 26 properties property NOUN admet-9 94 27     SPACE admet-9 94 28 in in ADP admet-9 94 29     SPACE admet-9 94 30 terms term NOUN admet-9 94 31     SPACE admet-9 94 32 of of ADP admet-9 94 33     SPACE admet-9 94 34 physicochemical physicochemical ADJ admet-9 94 35     SPACE admet-9 94 36 properties property NOUN admet-9 94 37 , , PUNCT admet-9 94 38     SPACE admet-9 94 39 such such ADJ admet-9 94 40     SPACE admet-9 94 41 as as ADP admet-9 94 42     SPACE admet-9 94 43 solubility solubility NOUN admet-9 94 44 , , PUNCT admet-9 94 45     SPACE admet-9 94 46 log log NOUN admet-9 94 47     SPACE admet-9 94 48 d d PROPN admet-9 94 49 , , PUNCT admet-9 94 50     SPACE admet-9 94 51 in in ADP admet-9 94 52     SPACE admet-9 94 53 vitro vitro VERB admet-9 94 54     SPACE admet-9 94 55 microsomal microsomal ADJ admet-9 94 56     SPACE admet-9 94 57 stability stability NOUN admet-9 94 58     SPACE admet-9 94 59 ( ( PUNCT admet-9 94 60 clint clint NOUN admet-9 94 61 ) ) PUNCT admet-9 94 62 , , PUNCT admet-9 94 63     SPACE admet-9 94 64 and and CCONJ admet-9 94 65     SPACE admet-9 94 66 permeability permeability NOUN admet-9 94 67 / / SYM admet-9 94 68 efflux efflux NOUN admet-9 94 69     SPACE admet-9 94 70 data datum NOUN admet-9 94 71 , , PUNCT admet-9 94 72     SPACE admet-9 94 73 as as ADV admet-9 94 74     SPACE admet-9 94 75 well well ADV admet-9 94 76     SPACE admet-9 94 77 as as ADP admet-9 94 78     SPACE admet-9 94 79 high high ADJ admet-9 94 80     SPACE admet-9 94 81 in in ADP admet-9 94 82     SPACE admet-9 94 83 vivo vivo NOUN admet-9 94 84     SPACE admet-9 94 85 clearance clearance NOUN admet-9 94 86     SPACE admet-9 94 87 or or CCONJ admet-9 94 88     SPACE admet-9 94 89 low low ADJ admet-9 94 90     SPACE admet-9 94 91 bioavailability bioavailability NOUN admet-9 94 92 . . PUNCT admet-9 94 93     SPACE admet-9 95 1 if if SCONJ admet-9 95 2     SPACE admet-9 95 3 we we PRON admet-9 95 4     SPACE admet-9 95 5 use use VERB admet-9 95 6     SPACE admet-9 95 7 only only ADJ admet-9 95 8     SPACE admet-9 95 9 pk pk NOUN admet-9 95 10     SPACE admet-9 95 11 data datum NOUN admet-9 95 12     SPACE admet-9 95 13 to to PART admet-9 95 14     SPACE admet-9 95 15 screen screen VERB admet-9 95 16     SPACE admet-9 95 17 the the DET admet-9 95 18     SPACE admet-9 95 19 compounds compound NOUN admet-9 95 20 , , PUNCT admet-9 95 21     SPACE admet-9 95 22 some some DET admet-9 95 23     SPACE admet-9 95 24 potential potential ADJ admet-9 95 25     SPACE admet-9 95 26 drug‐like drug‐like NOUN admet-9 95 27     SPACE admet-9 95 28 compounds compound NOUN admet-9 95 29     SPACE admet-9 95 30 might might AUX admet-9 95 31     SPACE admet-9 95 32 be be AUX admet-9 95 33     SPACE admet-9 95 34 discarded discard VERB admet-9 95 35 . . PUNCT admet-9 95 36     SPACE admet-9 95 37 in in ADP admet-9 95 38     SPACE admet-9 95 39 other other ADJ admet-9 95 40     SPACE admet-9 95 41 words word NOUN admet-9 95 42 , , PUNCT admet-9 95 43     SPACE admet-9 95 44 the the DET admet-9 95 45     SPACE admet-9 95 46 atorvastatin‐like atorvastatin‐like ADJ admet-9 95 47     SPACE admet-9 95 48 compounds compound NOUN admet-9 95 49     SPACE admet-9 95 50 would would AUX admet-9 95 51     SPACE admet-9 95 52 never never ADV admet-9 95 53     SPACE admet-9 95 54 have have AUX admet-9 95 55     SPACE admet-9 95 56 become become VERB admet-9 95 57     SPACE admet-9 95 58 good good ADJ admet-9 95 59     SPACE admet-9 95 60 drugs drug NOUN admet-9 95 61     SPACE admet-9 95 62 from from ADP admet-9 95 63     SPACE admet-9 95 64 the the DET admet-9 95 65     SPACE admet-9 95 66 sole sole ADJ admet-9 95 67     SPACE admet-9 95 68 view view NOUN admet-9 95 69     SPACE admet-9 95 70 of of ADP admet-9 95 71     SPACE admet-9 95 72 pk pk NOUN admet-9 95 73     SPACE admet-9 95 74 profiles profile NOUN admet-9 95 75 . . PUNCT admet-9 95 76     SPACE admet-9 96 1 these these DET admet-9 96 2     SPACE admet-9 96 3 examples example NOUN admet-9 96 4     SPACE admet-9 96 5 suggest suggest VERB admet-9 96 6     SPACE admet-9 96 7 that that SCONJ admet-9 96 8     SPACE admet-9 96 9 a a DET admet-9 96 10     SPACE admet-9 96 11 better well ADJ admet-9 96 12     SPACE admet-9 96 13 understanding understanding NOUN admet-9 96 14     SPACE admet-9 96 15 of of ADP admet-9 96 16     SPACE admet-9 96 17 in in ADP admet-9 96 18     SPACE admet-9 96 19 vitro‐in vitro‐in ADJ admet-9 96 20     SPACE admet-9 96 21 vivo vivo ADJ admet-9 96 22     SPACE admet-9 96 23 correlation correlation NOUN admet-9 96 24     SPACE admet-9 96 25 and and CCONJ admet-9 96 26     SPACE admet-9 96 27 frontloading frontloade VERB admet-9 96 28     SPACE admet-9 96 29 pk pk NOUN admet-9 96 30 / / SYM admet-9 96 31 pd pd NOUN admet-9 96 32     SPACE admet-9 96 33 is be AUX admet-9 96 34     SPACE admet-9 96 35 crucial crucial ADJ admet-9 96 36     SPACE admet-9 96 37 for for ADP admet-9 96 38     SPACE admet-9 96 39 compound compound NOUN admet-9 96 40     SPACE admet-9 96 41 selection selection NOUN admet-9 96 42     SPACE admet-9 96 43 even even ADV admet-9 96 44     SPACE admet-9 96 45 at at ADP admet-9 96 46     SPACE admet-9 96 47 an an DET admet-9 96 48     SPACE admet-9 96 49 early early ADJ admet-9 96 50     SPACE admet-9 96 51 stage stage NOUN admet-9 96 52 . . PUNCT admet-9 96 53     SPACE admet-9 96 54 obviously obviously ADV admet-9 96 55 , , PUNCT admet-9 96 56     SPACE admet-9 96 57 a a DET admet-9 96 58     SPACE admet-9 96 59 super super NOUN admet-9 96 60     SPACE admet-9 96 61 pd pd NOUN admet-9 96 62     SPACE admet-9 96 63 can can AUX admet-9 96 64     SPACE admet-9 96 65 save save VERB admet-9 96 66     SPACE admet-9 96 67 a a DET admet-9 96 68     SPACE admet-9 96 69 poor poor ADJ admet-9 96 70     SPACE admet-9 96 71 pk pk NOUN admet-9 96 72     SPACE admet-9 96 73 as as ADV admet-9 96 74     SPACE admet-9 96 75 long long ADJ admet-9 96 76     SPACE admet-9 96 77 as as ADP admet-9 96 78     SPACE admet-9 96 79 the the DET admet-9 96 80     SPACE admet-9 96 81 pd pd NOUN admet-9 96 82     SPACE admet-9 96 83 effect effect NOUN admet-9 96 84     SPACE admet-9 96 85 is be AUX admet-9 96 86     SPACE admet-9 96 87 notable notable ADJ admet-9 96 88 . . PUNCT admet-9 96 89         SPACE admet-9 96 90 wan wan PROPN admet-9 96 91         SPACE admet-9 96 92 admet admet X admet-9 96 93     SPACE admet-9 96 94 & & CCONJ admet-9 96 95     SPACE admet-9 96 96 dmpk dmpk VERB admet-9 96 97     SPACE admet-9 96 98 1(3 1(3 NUM admet-9 96 99 ) ) PUNCT admet-9 96 100     SPACE admet-9 96 101 ( ( PUNCT admet-9 96 102 2013 2013 NUM admet-9 96 103 ) ) PUNCT admet-9 96 104     SPACE admet-9 96 105 19‐28 19‐28 NUM admet-9 96 106     SPACE admet-9 96 107 26 26 NUM admet-9 96 108                 SPACE admet-9 96 109 figure figure NOUN admet-9 96 110     SPACE admet-9 96 111 3 3 NUM admet-9 96 112 : : PUNCT admet-9 96 113     SPACE admet-9 96 114 distribution distribution NOUN admet-9 96 115     SPACE admet-9 96 116 of of ADP admet-9 96 117     SPACE admet-9 96 118 human human ADJ admet-9 96 119     SPACE admet-9 96 120 clearance clearance NOUN admet-9 96 121     SPACE admet-9 96 122 and and CCONJ admet-9 96 123     SPACE admet-9 96 124 bioavailability bioavailability NOUN admet-9 96 125     SPACE admet-9 96 126 of of ADP admet-9 96 127     SPACE admet-9 96 128 market market NOUN admet-9 96 129     SPACE admet-9 96 130 drugs drug NOUN admet-9 96 131             SPACE admet-9 96 132 5 5 NUM admet-9 96 133 . . PUNCT admet-9 96 134     SPACE admet-9 96 135 concluding conclude VERB admet-9 96 136     SPACE admet-9 96 137 remarks remark VERB admet-9 96 138     SPACE admet-9 96 139 drug drug NOUN admet-9 96 140     SPACE admet-9 96 141 discovery discovery NOUN admet-9 96 142     SPACE admet-9 96 143 and and CCONJ admet-9 96 144     SPACE admet-9 96 145 development development NOUN admet-9 96 146     SPACE admet-9 96 147 are be AUX admet-9 96 148     SPACE admet-9 96 149 a a DET admet-9 96 150     SPACE admet-9 96 151 high‐risk high‐risk NOUN admet-9 96 152 , , PUNCT admet-9 96 153     SPACE admet-9 96 154 high‐cost high‐cost NOUN admet-9 96 155     SPACE admet-9 96 156 but but CCONJ admet-9 96 157     SPACE admet-9 96 158 highly highly ADV admet-9 96 159     SPACE admet-9 96 160 rewarding reward VERB admet-9 96 161     SPACE admet-9 96 162 business business NOUN admet-9 96 163 . . PUNCT admet-9 96 164     SPACE admet-9 97 1 many many ADJ admet-9 97 2     SPACE admet-9 97 3 resources resource NOUN admet-9 97 4     SPACE admet-9 97 5 are be AUX admet-9 97 6     SPACE admet-9 97 7 invested invest VERB admet-9 97 8 , , PUNCT admet-9 97 9     SPACE admet-9 97 10 and and CCONJ admet-9 97 11     SPACE admet-9 97 12 thus thus ADV admet-9 97 13     SPACE admet-9 97 14 wasted waste VERB admet-9 97 15     SPACE admet-9 97 16 on on ADP admet-9 97 17 , , PUNCT admet-9 97 18     SPACE admet-9 97 19 candidate candidate NOUN admet-9 97 20     SPACE admet-9 97 21 products product NOUN admet-9 97 22     SPACE admet-9 97 23 that that PRON admet-9 97 24     SPACE admet-9 97 25 are be AUX admet-9 97 26     SPACE admet-9 97 27 subsequently subsequently ADV admet-9 97 28     SPACE admet-9 97 29 found find VERB admet-9 97 30     SPACE admet-9 97 31 to to PART admet-9 97 32     SPACE admet-9 97 33 have have VERB admet-9 97 34     SPACE admet-9 97 35 unacceptable unacceptable ADJ admet-9 97 36     SPACE admet-9 97 37 profiles profile NOUN admet-9 97 38     SPACE admet-9 97 39 when when SCONJ admet-9 97 40     SPACE admet-9 97 41 evaluated evaluate VERB admet-9 97 42     SPACE admet-9 97 43 in in ADP admet-9 97 44     SPACE admet-9 97 45 human human NOUN admet-9 97 46     SPACE admet-9 97 47 – – PUNCT admet-9 97 48     SPACE admet-9 97 49 only only ADV admet-9 97 50     SPACE admet-9 97 51 less less ADJ admet-9 97 52     SPACE admet-9 97 53 than than ADP admet-9 97 54     SPACE admet-9 97 55 10 10 NUM admet-9 97 56 % % NOUN admet-9 97 57     SPACE admet-9 97 58 of of ADP admet-9 97 59     SPACE admet-9 97 60 inds ind VERB admet-9 97 61     SPACE admet-9 97 62 from from ADP admet-9 97 63     SPACE admet-9 97 64 nmes nme NOUN admet-9 97 65     SPACE admet-9 97 66 progress progress NOUN admet-9 97 67     SPACE admet-9 97 68 beyond beyond ADP admet-9 97 69     SPACE admet-9 97 70 the the DET admet-9 97 71     SPACE admet-9 97 72 submission submission NOUN admet-9 97 73     SPACE admet-9 97 74 of of ADP admet-9 97 75     SPACE admet-9 97 76 new new ADJ admet-9 97 77     SPACE admet-9 97 78 drug drug NOUN admet-9 97 79     SPACE admet-9 97 80 application application NOUN admet-9 97 81     SPACE admet-9 97 82 ( ( PUNCT admet-9 97 83 nda nda PROPN admet-9 97 84 ) ) PUNCT admet-9 97 85     SPACE admet-9 98 1 according accord VERB admet-9 98 2     SPACE admet-9 98 3 to to ADP admet-9 98 4     SPACE admet-9 98 5 the the DET admet-9 98 6     SPACE admet-9 98 7 fda fda PROPN admet-9 98 8 ’s ’s NOUN admet-9 98 9     SPACE admet-9 98 10 report report NOUN admet-9 98 11     SPACE admet-9 98 12 [ [ X admet-9 98 13 8 8 NUM admet-9 98 14 ] ] PUNCT admet-9 98 15 . . PUNCT admet-9 98 16     SPACE admet-9 99 1 as as ADP admet-9 99 2     SPACE admet-9 99 3 a a DET admet-9 99 4     SPACE admet-9 99 5 very very ADV admet-9 99 6     SPACE admet-9 99 7 comprehensive comprehensive ADJ admet-9 99 8     SPACE admet-9 99 9 and and CCONJ admet-9 99 10     SPACE admet-9 99 11 important important ADJ admet-9 99 12     SPACE admet-9 99 13 science science NOUN admet-9 99 14     SPACE admet-9 99 15 and and CCONJ admet-9 99 16     SPACE admet-9 99 17 technology technology NOUN admet-9 99 18     SPACE admet-9 99 19 platform platform NOUN admet-9 99 20     SPACE admet-9 99 21 bridging bridging NOUN admet-9 99 22     SPACE admet-9 99 23 efficacy efficacy NOUN admet-9 99 24     SPACE admet-9 99 25 and and CCONJ admet-9 99 26     SPACE admet-9 99 27 safety safety NOUN admet-9 99 28 , , PUNCT admet-9 99 29     SPACE admet-9 99 30 dmpk dmpk NOUN admet-9 99 31     SPACE admet-9 99 32 has have AUX admet-9 99 33     SPACE admet-9 99 34 become become VERB admet-9 99 35     SPACE admet-9 99 36 a a DET admet-9 99 37     SPACE admet-9 99 38 discovery discovery NOUN admet-9 99 39     SPACE admet-9 99 40 function function NOUN admet-9 99 41     SPACE admet-9 99 42 to to ADP admet-9 99 43     SPACE admet-9 99 44 optimise optimise VERB admet-9 99 45     SPACE admet-9 99 46 adme adme NOUN admet-9 99 47     SPACE admet-9 99 48 properties property NOUN admet-9 99 49     SPACE admet-9 99 50 in in ADP admet-9 99 51     SPACE admet-9 99 52 drug drug NOUN admet-9 99 53     SPACE admet-9 99 54 design design NOUN admet-9 99 55 , , PUNCT admet-9 99 56     SPACE admet-9 99 57 to to PART admet-9 99 58     SPACE admet-9 99 59 reduce reduce VERB admet-9 99 60     SPACE admet-9 99 61 attrition attrition NOUN admet-9 99 62     SPACE admet-9 99 63 rates rate NOUN admet-9 99 64 . . PUNCT admet-9 99 65     SPACE admet-9 100 1 recent recent ADJ admet-9 100 2     SPACE admet-9 100 3 studies study NOUN admet-9 100 4     SPACE admet-9 100 5 have have AUX admet-9 100 6     SPACE admet-9 100 7 demonstrated demonstrate VERB admet-9 100 8     SPACE admet-9 100 9 that that SCONJ admet-9 100 10     SPACE admet-9 100 11 it it PRON admet-9 100 12     SPACE admet-9 100 13 is be AUX admet-9 100 14     SPACE admet-9 100 15 viable viable ADJ admet-9 100 16     SPACE admet-9 100 17 to to PART admet-9 100 18     SPACE admet-9 100 19 implement implement VERB admet-9 100 20     SPACE admet-9 100 21 high‐throughput high‐throughput ADJ admet-9 100 22     SPACE admet-9 100 23 cutting‐edge cutting‐edge NOUN admet-9 100 24     SPACE admet-9 100 25 technologies technology NOUN admet-9 100 26     SPACE admet-9 100 27 and and CCONJ admet-9 100 28     SPACE admet-9 100 29 cost‐effective cost‐effective ADJ admet-9 100 30     SPACE admet-9 100 31 adme adme NOUN admet-9 100 32 / / SYM admet-9 100 33 dmpk dmpk NOUN admet-9 100 34     SPACE admet-9 100 35 screening screening NOUN admet-9 100 36     SPACE admet-9 100 37 assays assay NOUN admet-9 100 38 , , PUNCT admet-9 100 39     SPACE admet-9 100 40 and and CCONJ admet-9 100 41     SPACE admet-9 100 42 design design NOUN admet-9 100 43     SPACE admet-9 100 44 relevant relevant ADJ admet-9 100 45     SPACE admet-9 100 46 studies study NOUN admet-9 100 47     SPACE admet-9 100 48 to to PART admet-9 100 49     SPACE admet-9 100 50 address address VERB admet-9 100 51     SPACE admet-9 100 52 various various ADJ admet-9 100 53     SPACE admet-9 100 54 adme adme NOUN admet-9 100 55     SPACE admet-9 100 56 issues issue NOUN admet-9 100 57     SPACE admet-9 100 58 at at ADP admet-9 100 59     SPACE admet-9 100 60 different different ADJ admet-9 100 61     SPACE admet-9 100 62 stages stage NOUN admet-9 100 63     SPACE admet-9 100 64 for for ADP admet-9 100 65     SPACE admet-9 100 66 de‐risking de‐riske VERB admet-9 100 67     SPACE admet-9 100 68 the the DET admet-9 100 69     SPACE admet-9 100 70 investment investment NOUN admet-9 100 71     SPACE admet-9 100 72 and and CCONJ admet-9 100 73     SPACE admet-9 100 74 avoiding avoid VERB admet-9 100 75     SPACE admet-9 100 76 development development NOUN admet-9 100 77     SPACE admet-9 100 78 mistakes mistake NOUN admet-9 100 79     SPACE admet-9 100 80 early early ADV admet-9 100 81 . . PUNCT admet-9 100 82         SPACE admet-9 101 1 apparently apparently ADV admet-9 101 2 , , PUNCT admet-9 101 3     SPACE admet-9 101 4 at at ADP admet-9 101 5     SPACE admet-9 101 6 drug drug NOUN admet-9 101 7     SPACE admet-9 101 8 discovery discovery NOUN admet-9 101 9     SPACE admet-9 101 10 stage stage NOUN admet-9 101 11 , , PUNCT admet-9 101 12     SPACE admet-9 101 13 a a DET admet-9 101 14     SPACE admet-9 101 15 better well ADJ admet-9 101 16     SPACE admet-9 101 17 understanding understanding NOUN admet-9 101 18     SPACE admet-9 101 19 of of ADP admet-9 101 20     SPACE admet-9 101 21 sar sar NOUN admet-9 101 22     SPACE admet-9 101 23 and and CCONJ admet-9 101 24     SPACE admet-9 101 25 in in ADP admet-9 101 26     SPACE admet-9 101 27 vitro‐in vitro‐in ADJ admet-9 101 28     SPACE admet-9 101 29 vivo vivo ADJ admet-9 101 30     SPACE admet-9 101 31 correlations correlation NOUN admet-9 101 32 , , PUNCT admet-9 101 33     SPACE admet-9 101 34 and and CCONJ admet-9 101 35     SPACE admet-9 101 36 more more ADJ admet-9 101 37     SPACE admet-9 101 38 input input NOUN admet-9 101 39     SPACE admet-9 101 40 on on ADP admet-9 101 41     SPACE admet-9 101 42 drug drug NOUN admet-9 101 43     SPACE admet-9 101 44 design design NOUN admet-9 101 45     SPACE admet-9 101 46 can can AUX admet-9 101 47     SPACE admet-9 101 48 be be AUX admet-9 101 49     SPACE admet-9 101 50 anticipated anticipate VERB admet-9 101 51 . . PUNCT admet-9 101 52     SPACE admet-9 102 1 moreover moreover ADV admet-9 102 2 , , PUNCT admet-9 102 3     SPACE admet-9 102 4 frontloading frontloade VERB admet-9 102 5     SPACE admet-9 102 6 pk pk NOUN admet-9 102 7 / / SYM admet-9 102 8 pd pd NOUN admet-9 102 9     SPACE admet-9 102 10 for for ADP admet-9 102 11     SPACE admet-9 102 12 a a DET admet-9 102 13     SPACE admet-9 102 14 better well ADJ admet-9 102 15     SPACE admet-9 102 16 understanding understanding NOUN admet-9 102 17     SPACE admet-9 102 18 of of ADP admet-9 102 19     SPACE admet-9 102 20 the the DET admet-9 102 21     SPACE admet-9 102 22 efficacy‐exposure efficacy‐exposure NOUN admet-9 102 23     SPACE admet-9 102 24 relationship relationship NOUN admet-9 102 25     SPACE admet-9 102 26 and and CCONJ admet-9 102 27     SPACE admet-9 102 28 dose dose NOUN admet-9 102 29     SPACE admet-9 102 30 prediction prediction NOUN admet-9 102 31     SPACE admet-9 102 32 as as ADP admet-9 102 33     SPACE admet-9 102 34 early early ADV admet-9 102 35     SPACE admet-9 102 36 as as SCONJ admet-9 102 37     SPACE admet-9 102 38 possible possible ADJ admet-9 102 39     SPACE admet-9 102 40 can can AUX admet-9 102 41     SPACE admet-9 102 42 benefit benefit VERB admet-9 102 43     SPACE admet-9 102 44 projects project NOUN admet-9 102 45 . . PUNCT admet-9 102 46     SPACE admet-9 103 1 the the DET admet-9 103 2     SPACE admet-9 103 3 integration integration NOUN admet-9 103 4     SPACE admet-9 103 5 of of ADP admet-9 103 6     SPACE admet-9 103 7 in in ADV admet-9 103 8     SPACE admet-9 103 9 vitro vitro VERB admet-9 103 10     SPACE admet-9 103 11 and and CCONJ admet-9 103 12     SPACE admet-9 103 13 in in ADP admet-9 103 14     SPACE admet-9 103 15 vivo vivo NOUN admet-9 103 16     SPACE admet-9 103 17 drug drug NOUN admet-9 103 18     SPACE admet-9 103 19 metabolism metabolism NOUN admet-9 103 20     SPACE admet-9 103 21 data datum NOUN admet-9 103 22     SPACE admet-9 103 23 with with ADP admet-9 103 24     SPACE admet-9 103 25 physicochemical physicochemical ADJ admet-9 103 26     SPACE admet-9 103 27 properties property NOUN admet-9 103 28     SPACE admet-9 103 29 as as ADV admet-9 103 30     SPACE admet-9 103 31 well well ADV admet-9 103 32     SPACE admet-9 103 33 as as ADP admet-9 103 34     SPACE admet-9 103 35 pk pk NOUN admet-9 103 36     SPACE admet-9 103 37 and and CCONJ admet-9 103 38     SPACE admet-9 103 39 pd pd PROPN admet-9 103 40     SPACE admet-9 103 41 data datum NOUN admet-9 103 42     SPACE admet-9 103 43 is be AUX admet-9 103 44     SPACE admet-9 103 45 highly highly ADV admet-9 103 46     SPACE admet-9 103 47 recommended recommend VERB admet-9 103 48     SPACE admet-9 103 49 for for ADP admet-9 103 50     SPACE admet-9 103 51 safety safety NOUN admet-9 103 52     SPACE admet-9 103 53 and and CCONJ admet-9 103 54     SPACE admet-9 103 55 toxicity toxicity NOUN admet-9 103 56     SPACE admet-9 103 57 liability liability NOUN admet-9 103 58     SPACE admet-9 103 59 evaluation evaluation NOUN admet-9 103 60 , , PUNCT admet-9 103 61     SPACE admet-9 103 62 e.g. e.g. ADV admet-9 103 63 , , PUNCT admet-9 103 64     SPACE admet-9 103 65 are be AUX admet-9 103 66     SPACE admet-9 103 67 there there ADV admet-9 103 68     SPACE admet-9 103 69 any any DET admet-9 103 70     SPACE admet-9 103 71 drug drug NOUN admet-9 103 72     SPACE admet-9 103 73 accumulations accumulation NOUN admet-9 103 74 ? ? PUNCT admet-9 103 75     SPACE admet-9 103 76 are be AUX admet-9 103 77     SPACE admet-9 103 78 there there PRON admet-9 103 79     SPACE admet-9 103 80 any any DET admet-9 103 81     SPACE admet-9 103 82 potential potential ADJ admet-9 103 83     SPACE admet-9 103 84 toxic toxic ADJ admet-9 103 85     SPACE admet-9 103 86 metabolites metabolite NOUN admet-9 103 87 ? ? PUNCT admet-9 103 88     SPACE admet-9 103 89 are be AUX admet-9 103 90     SPACE admet-9 103 91 there there PRON admet-9 103 92     SPACE admet-9 103 93 any any DET admet-9 103 94     SPACE admet-9 103 95 likely likely ADJ admet-9 103 96     SPACE admet-9 103 97 ddis ddi NOUN admet-9 103 98 ? ? PUNCT admet-9 103 99     SPACE admet-9 103 100 are be AUX admet-9 103 101     SPACE admet-9 103 102 estimated estimate VERB admet-9 103 103     SPACE admet-9 103 104 safety safety NOUN admet-9 103 105     SPACE admet-9 103 106 margins margin NOUN admet-9 103 107     SPACE admet-9 103 108 enough enough ADV admet-9 103 109 ? ? PUNCT admet-9 103 110     SPACE admet-9 103 111 these these DET admet-9 103 112     SPACE admet-9 103 113 safety‐related safety‐relate VERB admet-9 103 114     SPACE admet-9 103 115 questions question NOUN admet-9 103 116     SPACE admet-9 103 117 have have VERB admet-9 103 118     SPACE admet-9 103 119 to to PART admet-9 103 120     SPACE admet-9 103 121 be be AUX admet-9 103 122     SPACE admet-9 103 123 answered answer VERB admet-9 103 124     SPACE admet-9 103 125 as as ADP admet-9 103 126     SPACE admet-9 103 127 early early ADJ admet-9 103 128     SPACE admet-9 103 129 and and CCONJ admet-9 103 130     SPACE admet-9 103 131 clearly clearly ADV admet-9 103 132     SPACE admet-9 103 133 as as ADP admet-9 103 134     SPACE admet-9 103 135 possible possible ADJ admet-9 103 136     SPACE admet-9 103 137 to to PART admet-9 103 138     SPACE admet-9 103 139 de‐risk de‐risk VERB admet-9 103 140     SPACE admet-9 103 141 the the DET admet-9 103 142     SPACE admet-9 103 143 drug drug NOUN admet-9 103 144     SPACE admet-9 103 145 discovery discovery NOUN admet-9 103 146     SPACE admet-9 103 147 projects project NOUN admet-9 103 148 . . PUNCT admet-9 103 149     SPACE admet-9 104 1 another another DET admet-9 104 2     SPACE admet-9 104 3 concern concern NOUN admet-9 104 4     SPACE admet-9 104 5 is be AUX admet-9 104 6     SPACE admet-9 104 7 risk risk NOUN admet-9 104 8     SPACE admet-9 104 9 assessment assessment NOUN admet-9 104 10     SPACE admet-9 104 11 associated associate VERB admet-9 104 12     SPACE admet-9 104 13 with with ADP admet-9 104 14     SPACE admet-9 104 15 herg herg PROPN admet-9 104 16 , , PUNCT admet-9 104 17     SPACE admet-9 104 18 cyp cyp ADJ admet-9 104 19     SPACE admet-9 104 20 inhibition inhibition NOUN admet-9 104 21     SPACE admet-9 104 22 and and CCONJ admet-9 104 23     SPACE admet-9 104 24 induction induction NOUN admet-9 104 25 , , PUNCT admet-9 104 26     SPACE admet-9 104 27 metabolite metabolite NOUN admet-9 104 28     SPACE admet-9 104 29 profiling profiling NOUN admet-9 104 30     SPACE admet-9 104 31 and and CCONJ admet-9 104 32     SPACE admet-9 104 33 safety safety NOUN admet-9 104 34 , , PUNCT admet-9 104 35     SPACE admet-9 104 36 transporter transporter NOUN admet-9 104 37     SPACE admet-9 104 38 substrate substrate NOUN admet-9 104 39     SPACE admet-9 104 40 and and CCONJ admet-9 104 41     SPACE admet-9 104 42 inhibition inhibition NOUN admet-9 104 43 , , PUNCT admet-9 104 44     SPACE admet-9 104 45 safety safety NOUN admet-9 104 46     SPACE admet-9 104 47 margin margin NOUN admet-9 104 48 , , PUNCT admet-9 104 49     SPACE admet-9 104 50 etc etc X admet-9 104 51 . . X admet-9 104 52 , , PUNCT admet-9 104 53     SPACE admet-9 104 54 which which PRON admet-9 104 55     SPACE admet-9 104 56 is be AUX admet-9 104 57     SPACE admet-9 104 58 of of ADP admet-9 104 59     SPACE admet-9 104 60 ultimate ultimate ADJ admet-9 104 61     SPACE admet-9 104 62 importance importance NOUN admet-9 104 63     SPACE admet-9 104 64 for for ADP admet-9 104 65     SPACE admet-9 104 66 cs cs NOUN admet-9 104 67     SPACE admet-9 104 68 and and CCONJ admet-9 104 69     SPACE admet-9 104 70 decision‐making decision‐make VERB admet-9 104 71     SPACE admet-9 104 72 for for ADP admet-9 104 73     SPACE admet-9 104 74 the the DET admet-9 104 75     SPACE admet-9 104 76 ind‐enabling ind‐enabling ADJ admet-9 104 77     SPACE admet-9 104 78 package package NOUN admet-9 104 79 . . PUNCT admet-9 104 80     SPACE admet-9 105 1 future future ADJ admet-9 105 2     SPACE admet-9 105 3 adme adme NOUN admet-9 105 4     SPACE admet-9 105 5 studies study NOUN admet-9 105 6     SPACE admet-9 105 7 will will AUX admet-9 105 8     SPACE admet-9 105 9 continue continue VERB admet-9 105 10     SPACE admet-9 105 11 to to PART admet-9 105 12     SPACE admet-9 105 13 focus focus VERB admet-9 105 14     SPACE admet-9 105 15 on on ADP admet-9 105 16     SPACE admet-9 105 17 p450 p450 NUM admet-9 105 18     SPACE admet-9 105 19 enzymes enzyme NOUN admet-9 105 20     SPACE admet-9 105 21 and and CCONJ admet-9 105 22     SPACE admet-9 105 23 transporters transporter NOUN admet-9 105 24 ’ ' PUNCT admet-9 105 25     SPACE admet-9 105 26 impact impact NOUN admet-9 105 27     SPACE admet-9 105 28 on on ADP admet-9 105 29     SPACE admet-9 105 30 safe safe ADJ admet-9 105 31     SPACE admet-9 105 32 drug drug NOUN admet-9 105 33     SPACE admet-9 105 34 delivery delivery NOUN admet-9 105 35     SPACE admet-9 105 36 as as ADV admet-9 105 37     SPACE admet-9 105 38 well well ADV admet-9 105 39     SPACE admet-9 105 40 as as ADP admet-9 105 41     SPACE admet-9 105 42 accurate accurate ADJ admet-9 105 43     SPACE admet-9 105 44 prediction prediction NOUN admet-9 105 45     SPACE admet-9 105 46 of of ADP admet-9 105 47     SPACE admet-9 105 48 human human ADJ admet-9 105 49     SPACE admet-9 105 50 pk pk NOUN admet-9 105 51 , , PUNCT admet-9 105 52     SPACE admet-9 105 53 pk pk NOUN admet-9 105 54 / / SYM admet-9 105 55 pd pd NOUN admet-9 105 56     SPACE admet-9 105 57 modeling modeling NOUN admet-9 105 58     SPACE admet-9 105 59 and and CCONJ admet-9 105 60     SPACE admet-9 105 61 optimum optimum ADJ admet-9 105 62     SPACE admet-9 105 63 clinical clinical ADJ admet-9 105 64     SPACE admet-9 105 65 dosage dosage NOUN admet-9 105 66 . . PUNCT admet-9 105 67             SPACE admet-9 106 1 on on ADP admet-9 106 2     SPACE admet-9 106 3 the the DET admet-9 106 4     SPACE admet-9 106 5 other other ADJ admet-9 106 6     SPACE admet-9 106 7 hand hand NOUN admet-9 106 8 , , PUNCT admet-9 106 9     SPACE admet-9 106 10 from from ADP admet-9 106 11     SPACE admet-9 106 12 the the DET admet-9 106 13     SPACE admet-9 106 14 point point NOUN admet-9 106 15     SPACE admet-9 106 16 of of ADP admet-9 106 17     SPACE admet-9 106 18 view view NOUN admet-9 106 19     SPACE admet-9 106 20 of of ADP admet-9 106 21     SPACE admet-9 106 22 regulatory regulatory ADJ admet-9 106 23     SPACE admet-9 106 24 review review NOUN admet-9 106 25 , , PUNCT admet-9 106 26     SPACE admet-9 106 27 the the DET admet-9 106 28     SPACE admet-9 106 29 fda fda PROPN admet-9 106 30     SPACE admet-9 106 31 has have AUX admet-9 106 32     SPACE admet-9 106 33 been be AUX admet-9 106 34     SPACE admet-9 106 35 becoming become VERB admet-9 106 36     SPACE admet-9 106 37 increasingly increasingly ADV admet-9 106 38     SPACE admet-9 106 39 conservative conservative NOUN admet-9 106 40     SPACE admet-9 106 41 than than ADP admet-9 106 42     SPACE admet-9 106 43 ever ever ADV admet-9 106 44 , , PUNCT admet-9 106 45     SPACE admet-9 106 46 except except SCONJ admet-9 106 47     SPACE admet-9 106 48 for for ADP admet-9 106 49     SPACE admet-9 106 50 oncology oncology NOUN admet-9 106 51     SPACE admet-9 106 52 and and CCONJ admet-9 106 53     SPACE admet-9 106 54 life‐threatening life‐threatening NOUN admet-9 106 55     SPACE admet-9 106 56 diseases disease NOUN admet-9 106 57     SPACE admet-9 106 58 where where SCONJ admet-9 106 59     SPACE admet-9 106 60 a a DET admet-9 106 61     SPACE admet-9 106 62 risk‐benefit risk‐benefit NOUN admet-9 106 63     SPACE admet-9 106 64 assessment assessment NOUN admet-9 106 65     SPACE admet-9 106 66 can can AUX admet-9 106 67     SPACE admet-9 106 68 be be AUX admet-9 106 69     SPACE admet-9 106 70 considered consider VERB admet-9 106 71 . . PUNCT admet-9 106 72     SPACE admet-9 107 1 if if SCONJ admet-9 107 2     SPACE admet-9 107 3 a a DET admet-9 107 4     SPACE admet-9 107 5 drug drug NOUN admet-9 107 6     SPACE admet-9 107 7 is be AUX admet-9 107 8     SPACE admet-9 107 9 toxic toxic ADJ admet-9 107 10     SPACE admet-9 107 11 at at ADP admet-9 107 12     SPACE admet-9 107 13 clinically clinically ADV admet-9 107 14     SPACE admet-9 107 15 relevant relevant ADJ admet-9 107 16     SPACE admet-9 107 17 doses dose NOUN admet-9 107 18 , , PUNCT admet-9 107 19     SPACE admet-9 107 20 the the DET admet-9 107 21     SPACE admet-9 107 22 ind ind NOUN admet-9 107 23     SPACE admet-9 107 24 may may AUX admet-9 107 25     SPACE admet-9 107 26 never never ADV admet-9 107 27     SPACE admet-9 107 28 go go VERB admet-9 107 29     SPACE admet-9 107 30 forward forward ADV admet-9 107 31 . . PUNCT admet-9 107 32     SPACE admet-9 107 33 therefore therefore ADV admet-9 107 34 , , PUNCT admet-9 107 35     SPACE admet-9 107 36 a a DET admet-9 107 37     SPACE admet-9 107 38 complete complete ADJ admet-9 107 39     SPACE admet-9 107 40 study study NOUN admet-9 107 41 / / SYM admet-9 107 42 data data NOUN admet-9 107 43     SPACE admet-9 107 44 package package NOUN admet-9 107 45     SPACE admet-9 107 46 including include VERB admet-9 107 47     SPACE admet-9 107 48 as as ADV admet-9 107 49     SPACE admet-9 107 50 much much ADJ admet-9 107 51     SPACE admet-9 107 52 detailed detailed ADJ admet-9 107 53     SPACE admet-9 107 54 toxicity toxicity NOUN admet-9 107 55     SPACE admet-9 107 56 information information NOUN admet-9 107 57     SPACE admet-9 107 58 as as ADP admet-9 107 59     SPACE admet-9 107 60 possible possible ADJ admet-9 107 61     SPACE admet-9 107 62 can can AUX admet-9 107 63     SPACE admet-9 107 64 facilitate facilitate VERB admet-9 107 65     SPACE admet-9 107 66 ind ind PROPN admet-9 107 67     SPACE admet-9 107 68 filing filing NOUN admet-9 107 69     SPACE admet-9 107 70 and and CCONJ admet-9 107 71     SPACE admet-9 107 72 increase increase VERB admet-9 107 73     SPACE admet-9 107 74 the the DET admet-9 107 75     SPACE admet-9 107 76 clinical clinical ADJ admet-9 107 77     SPACE admet-9 107 78 trial trial NOUN admet-9 107 79     SPACE admet-9 107 80 success success NOUN admet-9 107 81     SPACE admet-9 107 82 rate rate NOUN admet-9 107 83 , , PUNCT admet-9 107 84     SPACE admet-9 107 85 which which PRON admet-9 107 86     SPACE admet-9 107 87 should should AUX admet-9 107 88     SPACE admet-9 107 89 cover cover VERB admet-9 107 90     SPACE admet-9 107 91 pharmacology pharmacology NOUN admet-9 107 92     SPACE admet-9 107 93 ( ( PUNCT admet-9 107 94 efficacy efficacy NOUN admet-9 107 95     SPACE admet-9 107 96 and and CCONJ admet-9 107 97     SPACE admet-9 107 98 animal animal NOUN admet-9 107 99     SPACE admet-9 107 100 admet admet NOUN admet-9 107 101     SPACE admet-9 107 102 & & CCONJ admet-9 107 103     SPACE admet-9 107 104 dmpk dmpk VERB admet-9 107 105     SPACE admet-9 107 106 1(3 1(3 NUM admet-9 107 107 ) ) PUNCT admet-9 107 108     SPACE admet-9 107 109 ( ( PUNCT admet-9 107 110 2013 2013 NUM admet-9 107 111 ) ) PUNCT admet-9 107 112     SPACE admet-9 107 113 19‐28 19‐28 NUM admet-9 107 114     SPACE admet-9 107 115 adme adme NOUN admet-9 107 116     SPACE admet-9 107 117 tests test NOUN admet-9 107 118     SPACE admet-9 107 119 for for ADP admet-9 107 120     SPACE admet-9 107 121 preclinical preclinical ADJ admet-9 107 122     SPACE admet-9 107 123 studies study NOUN admet-9 107 124     SPACE admet-9 107 125 doi doi NOUN admet-9 107 126 : : PUNCT admet-9 107 127     SPACE admet-9 107 128 10.5599 10.5599 NUM admet-9 107 129 / / SYM admet-9 107 130 admet.1.3.9 admet.1.3.9 NOUN admet-9 107 131     SPACE admet-9 107 132 27 27 NUM admet-9 107 133     SPACE admet-9 107 134 proof proof NOUN admet-9 107 135     SPACE admet-9 107 136 of of ADP admet-9 107 137     SPACE admet-9 107 138 principle principle NOUN admet-9 107 139 ) ) PUNCT admet-9 107 140     SPACE admet-9 107 141 studies study NOUN admet-9 107 142 , , PUNCT admet-9 107 143     SPACE admet-9 107 144 a a DET admet-9 107 145     SPACE admet-9 107 146 rodent rodent ADJ admet-9 107 147     SPACE admet-9 107 148 general general ADJ admet-9 107 149     SPACE admet-9 107 150 toxicology toxicology NOUN admet-9 107 151     SPACE admet-9 107 152 study study NOUN admet-9 107 153     SPACE admet-9 107 154 of of ADP admet-9 107 155     SPACE admet-9 107 156 at at ADP admet-9 107 157     SPACE admet-9 107 158 least least ADJ admet-9 107 159     SPACE admet-9 107 160 a a DET admet-9 107 161     SPACE admet-9 107 162 14‐day 14‐day NOUN admet-9 107 163     SPACE admet-9 107 164 duration duration NOUN admet-9 107 165 , , PUNCT admet-9 107 166     SPACE admet-9 107 167 a a DET admet-9 107 168     SPACE admet-9 107 169 non‐rodent non‐rodent ADJ admet-9 107 170     SPACE admet-9 107 171 general general ADJ admet-9 107 172     SPACE admet-9 107 173 toxicology toxicology NOUN admet-9 107 174     SPACE admet-9 107 175 study study NOUN admet-9 107 176     SPACE admet-9 107 177 of of ADP admet-9 107 178     SPACE admet-9 107 179 at at ADP admet-9 107 180     SPACE admet-9 107 181 least least ADJ admet-9 107 182     SPACE admet-9 107 183 a a DET admet-9 107 184     SPACE admet-9 107 185 14‐day 14‐day NOUN admet-9 107 186     SPACE admet-9 107 187 duration duration NOUN admet-9 107 188 , , PUNCT admet-9 107 189     SPACE admet-9 107 190 genotoxicity genotoxicity NOUN admet-9 107 191     SPACE admet-9 107 192 studies study NOUN admet-9 107 193 , , PUNCT admet-9 107 194     SPACE admet-9 107 195 safety safety NOUN admet-9 107 196     SPACE admet-9 107 197 pharmacology pharmacology NOUN admet-9 107 198     SPACE admet-9 107 199 studies study NOUN admet-9 107 200 , , PUNCT admet-9 107 201     SPACE admet-9 107 202 adme adme NOUN admet-9 107 203 / / SYM admet-9 107 204 pk pk NOUN admet-9 107 205     SPACE admet-9 107 206 as as ADV admet-9 107 207     SPACE admet-9 107 208 well well ADV admet-9 107 209     SPACE admet-9 107 210 as as ADP admet-9 107 211     SPACE admet-9 107 212 bioanalytical bioanalytical ADJ admet-9 107 213     SPACE admet-9 107 214 validations validation NOUN admet-9 107 215 , , PUNCT admet-9 107 216     SPACE admet-9 107 217 etc etc X admet-9 107 218 . . X admet-9 107 219     SPACE admet-9 107 220 in in ADP admet-9 107 221     SPACE admet-9 107 222 the the DET admet-9 107 223     SPACE admet-9 107 224 end end NOUN admet-9 107 225 , , PUNCT admet-9 107 226     SPACE admet-9 107 227 we we PRON admet-9 107 228     SPACE admet-9 107 229 must must AUX admet-9 107 230     SPACE admet-9 107 231 clearly clearly ADV admet-9 107 232     SPACE admet-9 107 233 answer answer NOUN admet-9 107 234     SPACE admet-9 107 235 these these DET admet-9 107 236     SPACE admet-9 107 237 two two NUM admet-9 107 238     SPACE admet-9 107 239 key key ADJ admet-9 107 240     SPACE admet-9 107 241 questions question NOUN admet-9 107 242 : : PUNCT admet-9 107 243         SPACE admet-9 107 244 ( ( PUNCT admet-9 107 245 1 1 X admet-9 107 246 ) ) PUNCT admet-9 107 247     SPACE admet-9 107 248 is be AUX admet-9 107 249     SPACE admet-9 107 250 the the DET admet-9 107 251     SPACE admet-9 107 252 preclinical preclinical ADJ admet-9 107 253     SPACE admet-9 107 254 candidate candidate NOUN admet-9 107 255     SPACE admet-9 107 256 safe safe ADJ admet-9 107 257     SPACE admet-9 107 258 enough enough NOUN admet-9 107 259     SPACE admet-9 107 260 to to PART admet-9 107 261     SPACE admet-9 107 262 take take VERB admet-9 107 263     SPACE admet-9 107 264 into into ADP admet-9 107 265     SPACE admet-9 107 266 humans human NOUN admet-9 107 267 ? ? PUNCT admet-9 107 268         SPACE admet-9 108 1 ( ( PUNCT admet-9 108 2 2 2 NUM admet-9 108 3 ) ) PUNCT admet-9 108 4     SPACE admet-9 108 5 is be AUX admet-9 108 6     SPACE admet-9 108 7 the the DET admet-9 108 8     SPACE admet-9 108 9 preclinical preclinical ADJ admet-9 108 10     SPACE admet-9 108 11 candidate candidate NOUN admet-9 108 12     SPACE admet-9 108 13 effective effective ADJ admet-9 108 14     SPACE admet-9 108 15 in in ADP admet-9 108 16     SPACE admet-9 108 17 patients patient NOUN admet-9 108 18 ? ? PUNCT admet-9 108 19         SPACE admet-9 108 20 acknowledgements acknowledgement NOUN admet-9 108 21 : : PUNCT admet-9 108 22     SPACE admet-9 108 23 the the DET admet-9 108 24     SPACE admet-9 108 25 author author NOUN admet-9 108 26     SPACE admet-9 108 27 would would AUX admet-9 108 28     SPACE admet-9 108 29 like like VERB admet-9 108 30     SPACE admet-9 108 31 to to PART admet-9 108 32     SPACE admet-9 108 33 thank thank VERB admet-9 108 34     SPACE admet-9 108 35 dr dr PROPN admet-9 108 36 . . PROPN admet-9 108 37     SPACE admet-9 108 38 kin kin PROPN admet-9 108 39     SPACE admet-9 108 40 tam tam PROPN admet-9 108 41     SPACE admet-9 108 42 for for ADP admet-9 108 43     SPACE admet-9 108 44 proofreading proofreading NOUN admet-9 108 45     SPACE admet-9 108 46 this this DET admet-9 108 47     SPACE admet-9 108 48 article article NOUN admet-9 108 49     SPACE admet-9 108 50 with with ADP admet-9 108 51     SPACE admet-9 108 52 valuable valuable ADJ admet-9 108 53     SPACE admet-9 108 54 comments comment NOUN admet-9 108 55 . . PUNCT admet-9 108 56     SPACE admet-9 108 57 declaration declaration NOUN admet-9 108 58 : : PUNCT admet-9 108 59     SPACE admet-9 108 60 this this DET admet-9 108 61     SPACE admet-9 108 62 article article NOUN admet-9 108 63     SPACE admet-9 108 64 reflects reflect VERB admet-9 108 65     SPACE admet-9 108 66 the the DET admet-9 108 67     SPACE admet-9 108 68 author author NOUN admet-9 108 69 ’s ’s NOUN admet-9 108 70     SPACE admet-9 108 71 personal personal ADJ admet-9 108 72     SPACE admet-9 108 73 opinions opinion NOUN admet-9 108 74 . . PUNCT admet-9 108 75     SPACE admet-9 109 1 the the DET admet-9 109 2     SPACE admet-9 109 3 author author NOUN admet-9 109 4     SPACE admet-9 109 5 declares declare VERB admet-9 109 6     SPACE admet-9 109 7 that that SCONJ admet-9 109 8     SPACE admet-9 109 9 he he PRON admet-9 109 10     SPACE admet-9 109 11 has have VERB admet-9 109 12     SPACE admet-9 109 13 no no DET admet-9 109 14     SPACE admet-9 109 15 competing compete VERB admet-9 109 16     SPACE admet-9 109 17 financial financial ADJ admet-9 109 18     SPACE admet-9 109 19 interests interest NOUN admet-9 109 20 . . PUNCT admet-9 109 21         SPACE admet-9 110 1 references reference NOUN admet-9 110 2     SPACE admet-9 110 3 [ [ X admet-9 110 4 1 1 NUM admet-9 110 5 ] ] X admet-9 110 6 fda fda PROPN admet-9 110 7 : : PUNCT admet-9 110 8     SPACE admet-9 110 9 draft draft NOUN admet-9 110 10     SPACE admet-9 110 11 guidance guidance NOUN admet-9 110 12     SPACE admet-9 110 13 for for ADP admet-9 110 14     SPACE admet-9 110 15 industry industry NOUN admet-9 110 16 : : PUNCT admet-9 110 17     SPACE admet-9 110 18 drug drug NOUN admet-9 110 19     SPACE admet-9 110 20 interaction interaction NOUN admet-9 110 21     SPACE admet-9 110 22 studies study NOUN admet-9 110 23     SPACE admet-9 110 24 – – PUNCT admet-9 110 25     SPACE admet-9 110 26 study study NOUN admet-9 110 27     SPACE admet-9 110 28 design design NOUN admet-9 110 29 , , PUNCT admet-9 110 30     SPACE admet-9 110 31 data datum NOUN admet-9 110 32     SPACE admet-9 110 33 analysis analysis NOUN admet-9 110 34 , , PUNCT admet-9 110 35     SPACE admet-9 110 36 implications implication NOUN admet-9 110 37     SPACE admet-9 110 38 for for ADP admet-9 110 39     SPACE admet-9 110 40 dosing dose VERB admet-9 110 41 , , PUNCT admet-9 110 42     SPACE admet-9 110 43 and and CCONJ admet-9 110 44     SPACE admet-9 110 45 labeling labeling NOUN admet-9 110 46     SPACE admet-9 110 47 recommendation recommendation NOUN admet-9 110 48 , , PUNCT admet-9 110 49     SPACE admet-9 110 50 ( ( PUNCT admet-9 110 51 sept sept PROPN admet-9 110 52 . . PROPN admet-9 110 53     SPACE admet-9 110 54 2006 2006 NUM admet-9 110 55 ) ) PUNCT admet-9 110 56     SPACE admet-9 111 1 [ [ X admet-9 111 2 2 2 NUM admet-9 111 3 ] ] X admet-9 111 4 fda fda PROPN admet-9 111 5 : : PUNCT admet-9 111 6     SPACE admet-9 111 7 guidance guidance NOUN admet-9 111 8     SPACE admet-9 111 9 for for ADP admet-9 111 10     SPACE admet-9 111 11 industry industry NOUN admet-9 111 12 : : PUNCT admet-9 111 13     SPACE admet-9 111 14 drug drug NOUN admet-9 111 15     SPACE admet-9 111 16 interaction interaction NOUN admet-9 111 17     SPACE admet-9 111 18 studies study NOUN admet-9 111 19     SPACE admet-9 111 20 – – PUNCT admet-9 111 21     SPACE admet-9 111 22 study study NOUN admet-9 111 23     SPACE admet-9 111 24 design design NOUN admet-9 111 25 , , PUNCT admet-9 111 26     SPACE admet-9 111 27 data datum NOUN admet-9 111 28     SPACE admet-9 111 29 analysis analysis NOUN admet-9 111 30 , , PUNCT admet-9 111 31     SPACE admet-9 111 32 implications implication NOUN admet-9 111 33     SPACE admet-9 111 34 for for ADP admet-9 111 35     SPACE admet-9 111 36 dosing dosing NOUN admet-9 111 37 , , PUNCT admet-9 111 38     SPACE admet-9 111 39 and and CCONJ admet-9 111 40     SPACE admet-9 111 41 labeling labeling NOUN admet-9 111 42     SPACE admet-9 111 43 recommendation recommendation NOUN admet-9 111 44     SPACE admet-9 111 45 ( ( PUNCT admet-9 111 46 february february PROPN admet-9 111 47     SPACE admet-9 111 48 2012 2012 NUM admet-9 111 49 ) ) PUNCT admet-9 111 50     SPACE admet-9 112 1 [ [ X admet-9 112 2 3 3 X admet-9 112 3 ] ] X admet-9 112 4 fda fda PROPN admet-9 112 5 : : PUNCT admet-9 112 6     SPACE admet-9 112 7 guidance guidance NOUN admet-9 112 8     SPACE admet-9 112 9 for for ADP admet-9 112 10     SPACE admet-9 112 11 industry industry NOUN admet-9 112 12 : : PUNCT admet-9 112 13     SPACE admet-9 112 14 safety safety NOUN admet-9 112 15     SPACE admet-9 112 16 testing testing NOUN admet-9 112 17     SPACE admet-9 112 18 of of ADP admet-9 112 19     SPACE admet-9 112 20 drug drug NOUN admet-9 112 21     SPACE admet-9 112 22 metabolites metabolite NOUN admet-9 112 23     SPACE admet-9 112 24 ( ( PUNCT admet-9 112 25 february february PROPN admet-9 112 26     SPACE admet-9 112 27 2008 2008 NUM admet-9 112 28 ) ) PUNCT admet-9 112 29     SPACE admet-9 113 1 [ [ X admet-9 113 2 4 4 X admet-9 113 3 ] ] PUNCT admet-9 113 4 ich ich NOUN admet-9 113 5     SPACE admet-9 113 6 m3(r2 m3(r2 NOUN admet-9 113 7 ): ): PUNCT admet-9 113 8     SPACE admet-9 113 9 guidance guidance NOUN admet-9 113 10     SPACE admet-9 113 11 on on ADP admet-9 113 12     SPACE admet-9 113 13 nonclinical nonclinical ADJ admet-9 113 14     SPACE admet-9 113 15 safety safety NOUN admet-9 113 16     SPACE admet-9 113 17 studies study NOUN admet-9 113 18     SPACE admet-9 113 19 for for ADP admet-9 113 20     SPACE admet-9 113 21 the the DET admet-9 113 22     SPACE admet-9 113 23 conduct conduct NOUN admet-9 113 24     SPACE admet-9 113 25 of of ADP admet-9 113 26     SPACE admet-9 113 27 human human ADJ admet-9 113 28     SPACE admet-9 113 29 clinical clinical ADJ admet-9 113 30     SPACE admet-9 113 31 trials trial NOUN admet-9 113 32     SPACE admet-9 113 33 and and CCONJ admet-9 113 34     SPACE admet-9 113 35 marketing marketing NOUN admet-9 113 36     SPACE admet-9 113 37 authorization authorization NOUN admet-9 113 38     SPACE admet-9 113 39 for for ADP admet-9 113 40     SPACE admet-9 113 41 pharmaceuticals pharmaceutical NOUN admet-9 113 42     SPACE admet-9 113 43 ( ( PUNCT admet-9 113 44 june june PROPN admet-9 113 45     SPACE admet-9 113 46 2009 2009 NUM admet-9 113 47 ) ) PUNCT admet-9 113 48     SPACE admet-9 114 1 [ [ X admet-9 114 2 5 5 X admet-9 114 3 ] ] X admet-9 114 4 fda fda PROPN admet-9 114 5 : : PUNCT admet-9 114 6     SPACE admet-9 114 7 guidance guidance NOUN admet-9 114 8     SPACE admet-9 114 9 for for ADP admet-9 114 10     SPACE admet-9 114 11 industry industry NOUN admet-9 114 12     SPACE admet-9 114 13 s7b s7b NOUN admet-9 114 14     SPACE admet-9 114 15 nonclinical nonclinical ADJ admet-9 114 16     SPACE admet-9 114 17 evaluation evaluation NOUN admet-9 114 18     SPACE admet-9 114 19 of of ADP admet-9 114 20     SPACE admet-9 114 21 the the DET admet-9 114 22     SPACE admet-9 114 23 potential potential NOUN admet-9 114 24     SPACE admet-9 114 25 for for ADP admet-9 114 26     SPACE admet-9 114 27 delayed delay VERB admet-9 114 28     SPACE admet-9 114 29 ventricular ventricular ADJ admet-9 114 30     SPACE admet-9 114 31 repolarization repolarization NOUN admet-9 114 32     SPACE admet-9 114 33 ( ( PUNCT admet-9 114 34 qt qt NOUN admet-9 114 35     SPACE admet-9 114 36 interval interval NOUN admet-9 114 37     SPACE admet-9 114 38 prolongation prolongation NOUN admet-9 114 39 ) ) PUNCT admet-9 114 40     SPACE admet-9 114 41 by by ADP admet-9 114 42     SPACE admet-9 114 43 human human ADJ admet-9 114 44     SPACE admet-9 114 45 pharmaceuticals pharmaceutical NOUN admet-9 114 46     SPACE admet-9 114 47 ( ( PUNCT admet-9 114 48 2005 2005 NUM admet-9 114 49 ) ) PUNCT admet-9 114 50     SPACE admet-9 115 1 [ [ X admet-9 115 2 6 6 NUM admet-9 115 3 ] ] X admet-9 115 4 fda fda PROPN admet-9 115 5 : : PUNCT admet-9 115 6     SPACE admet-9 115 7 guidance guidance NOUN admet-9 115 8     SPACE admet-9 115 9 for for ADP admet-9 115 10     SPACE admet-9 115 11 industry industry NOUN admet-9 115 12     SPACE admet-9 115 13 bioanalytical bioanalytical ADJ admet-9 115 14     SPACE admet-9 115 15 method method NOUN admet-9 115 16     SPACE admet-9 115 17 validation validation NOUN admet-9 115 18     SPACE admet-9 115 19 ( ( PUNCT admet-9 115 20 2001 2001 NUM admet-9 115 21 ) ) PUNCT admet-9 115 22     SPACE admet-9 116 1 [ [ X admet-9 116 2 7 7 X admet-9 116 3 ] ] X admet-9 116 4 fda fda PROPN admet-9 116 5 : : PUNCT admet-9 116 6     SPACE admet-9 116 7 guidance guidance NOUN admet-9 116 8     SPACE admet-9 116 9 for for ADP admet-9 116 10     SPACE admet-9 116 11 industry industry NOUN admet-9 116 12     SPACE admet-9 116 13 content content NOUN admet-9 116 14     SPACE admet-9 116 15 and and CCONJ admet-9 116 16     SPACE admet-9 116 17 format format NOUN admet-9 116 18     SPACE admet-9 116 19 of of ADP admet-9 116 20     SPACE admet-9 116 21 investigational investigational ADJ admet-9 116 22     SPACE admet-9 116 23 new new ADJ admet-9 116 24     SPACE admet-9 116 25 drug drug NOUN admet-9 116 26     SPACE admet-9 116 27 applications application NOUN admet-9 116 28     SPACE admet-9 116 29 ( ( PUNCT admet-9 116 30 inds ind NOUN admet-9 116 31 ) ) PUNCT admet-9 116 32     SPACE admet-9 116 33 for for ADP admet-9 116 34     SPACE admet-9 116 35 phase phase NOUN admet-9 116 36     SPACE admet-9 116 37 1 1 NUM admet-9 116 38     SPACE admet-9 116 39 studies study NOUN admet-9 116 40     SPACE admet-9 116 41 of of ADP admet-9 116 42     SPACE admet-9 116 43 drugs drug NOUN admet-9 116 44 , , PUNCT admet-9 116 45     SPACE admet-9 116 46 including include VERB admet-9 116 47     SPACE admet-9 116 48 well‐characterized well‐characterize VERB admet-9 116 49 , , PUNCT admet-9 116 50     SPACE admet-9 116 51 therapeutic therapeutic ADJ admet-9 116 52 , , PUNCT admet-9 116 53     SPACE admet-9 116 54 biotechnology‐derived biotechnology‐derive VERB admet-9 116 55     SPACE admet-9 116 56 products product NOUN admet-9 116 57     SPACE admet-9 116 58 ( ( PUNCT admet-9 116 59 1997 1997 NUM admet-9 116 60 ) ) PUNCT admet-9 116 61     SPACE admet-9 117 1 [ [ X admet-9 117 2 8 8 NUM admet-9 117 3 ] ] X admet-9 117 4 fda fda PROPN admet-9 117 5 : : PUNCT admet-9 117 6     SPACE admet-9 117 7 guidance guidance NOUN admet-9 117 8     SPACE admet-9 117 9 for for ADP admet-9 117 10     SPACE admet-9 117 11 industry industry NOUN admet-9 117 12 , , PUNCT admet-9 117 13     SPACE admet-9 117 14 investigators investigator NOUN admet-9 117 15 , , PUNCT admet-9 117 16     SPACE admet-9 117 17 and and CCONJ admet-9 117 18     SPACE admet-9 117 19 reviewers reviewer NOUN admet-9 117 20     SPACE admet-9 117 21 ‐ ‐ NOUN admet-9 117 22     SPACE admet-9 117 23 exploratory exploratory ADJ admet-9 117 24     SPACE admet-9 117 25 ind ind NOUN admet-9 117 26     SPACE admet-9 117 27 studies study NOUN admet-9 117 28     SPACE admet-9 117 29 ( ( PUNCT admet-9 117 30 jan jan PROPN admet-9 117 31     SPACE admet-9 117 32 2006 2006 NUM admet-9 117 33 ) ) PUNCT admet-9 117 34     SPACE admet-9 118 1 [ [ X admet-9 118 2 9 9 NUM admet-9 118 3 ] ] SYM admet-9 118 4 g. g. NOUN admet-9 118 5     SPACE admet-9 118 6 lappin lappin NOUN admet-9 118 7 , , PUNCT admet-9 118 8     SPACE admet-9 118 9 m. m. NOUN admet-9 118 10     SPACE admet-9 118 11 seymour seymour ADJ admet-9 118 12 , , PUNCT admet-9 118 13     SPACE admet-9 118 14 bioanalysis bioanalysis NOUN admet-9 118 15     SPACE admet-9 118 16 2 2 NUM admet-9 118 17     SPACE admet-9 118 18 ( ( PUNCT admet-9 118 19 2010 2010 NUM admet-9 118 20 ) ) PUNCT admet-9 118 21     SPACE admet-9 118 22 1315‐1324 1315‐1324 NUM admet-9 118 23 . . PUNCT admet-9 118 24     SPACE admet-9 119 1 [ [ X admet-9 119 2 10 10 NUM admet-9 119 3 ] ] X admet-9 119 4 y.y y.y PROPN admet-9 119 5 . . PROPN admet-9 119 6     SPACE admet-9 119 7 lau lau PROPN admet-9 119 8 , , PUNCT admet-9 119 9     SPACE admet-9 119 10 h. h. PROPN admet-9 119 11     SPACE admet-9 119 12 okochi okochi PROPN admet-9 119 13 , , PUNCT admet-9 119 14     SPACE admet-9 119 15 y. y. PROPN admet-9 119 16     SPACE admet-9 119 17 huang huang PROPN admet-9 119 18     SPACE admet-9 119 19 and and CCONJ admet-9 119 20     SPACE admet-9 119 21 l.z l.z PROPN admet-9 119 22 . . PROPN admet-9 119 23     SPACE admet-9 119 24 benet benet PROPN admet-9 119 25 , , PUNCT admet-9 119 26     SPACE admet-9 119 27 drug drug NOUN admet-9 119 28     SPACE admet-9 119 29 metabolism metabolism NOUN admet-9 119 30     SPACE admet-9 119 31 and and CCONJ admet-9 119 32     SPACE admet-9 119 33 disposition disposition NOUN admet-9 119 34     SPACE admet-9 119 35 34 34 NUM admet-9 119 36     SPACE admet-9 119 37 ( ( PUNCT admet-9 119 38 2006 2006 NUM admet-9 119 39 ) ) PUNCT admet-9 119 40     SPACE admet-9 119 41 1175‐1181 1175‐1181 NUM admet-9 119 42 . . PUNCT admet-9 119 43     SPACE admet-9 120 1 [ [ X admet-9 120 2 11 11 NUM admet-9 120 3 ] ] X admet-9 120 4 h. h. PROPN admet-9 120 5     SPACE admet-9 120 6 lennernas lennernas PROPN admet-9 120 7 , , PUNCT admet-9 120 8     SPACE admet-9 120 9 clinical clinical ADJ admet-9 120 10     SPACE admet-9 120 11 pharmacokinetics pharmacokinetic NOUN admet-9 120 12     SPACE admet-9 120 13 42 42 NUM admet-9 120 14     SPACE admet-9 120 15 ( ( PUNCT admet-9 120 16 2003 2003 NUM admet-9 120 17 ) ) PUNCT admet-9 120 18     SPACE admet-9 120 19 1141‐1160 1141‐1160 NOUN admet-9 120 20 . . PUNCT admet-9 120 21     SPACE admet-9 121 1 [ [ X admet-9 121 2 12 12 NUM admet-9 121 3 ] ] X admet-9 121 4 l.s l.s PROPN admet-9 121 5 . . PROPN admet-9 121 6     SPACE admet-9 121 7 goodman goodman PROPN admet-9 121 8 , , PUNCT admet-9 121 9     SPACE admet-9 121 10 a. a. NOUN admet-9 121 11     SPACE admet-9 121 12 gilman gilman PROPN admet-9 121 13 , , PUNCT admet-9 121 14     SPACE admet-9 121 15 the the DET admet-9 121 16     SPACE admet-9 121 17 pharmacological pharmacological NOUN admet-9 121 18     SPACE admet-9 121 19 basis basis NOUN admet-9 121 20     SPACE admet-9 121 21 of of ADP admet-9 121 22     SPACE admet-9 121 23 therapeutics therapeutic NOUN admet-9 121 24 , , PUNCT admet-9 121 25     SPACE admet-9 121 26 mcgraw‐hill mcgraw‐hill NOUN admet-9 121 27     SPACE admet-9 121 28 publishers publisher NOUN admet-9 121 29 , , PUNCT admet-9 121 30     SPACE admet-9 121 31 new new ADJ admet-9 121 32     SPACE admet-9 121 33 york york PROPN admet-9 121 34 , , PUNCT admet-9 121 35     SPACE admet-9 121 36 usa usa PROPN admet-9 121 37 , , PUNCT admet-9 121 38     SPACE admet-9 121 39 2006 2006 NUM admet-9 121 40 . . PUNCT admet-9 121 41         SPACE admet-9 121 42 abbreviations abbreviation NOUN admet-9 121 43     SPACE admet-9 121 44 adme adme NOUN admet-9 121 45             SPACE admet-9 121 46 absorption absorption NOUN admet-9 121 47     SPACE admet-9 121 48 distribution distribution NOUN admet-9 121 49     SPACE admet-9 121 50 metabolism metabolism NOUN admet-9 121 51     SPACE admet-9 121 52 excretion excretion NOUN admet-9 121 53     SPACE admet-9 121 54 cro cro PROPN admet-9 121 55               SPACE admet-9 121 56 contact contact NOUN admet-9 121 57     SPACE admet-9 121 58 research research NOUN admet-9 121 59     SPACE admet-9 121 60 organization organization NOUN admet-9 121 61     SPACE admet-9 121 62 dmpk dmpk NOUN admet-9 121 63             SPACE admet-9 121 64 drug drug NOUN admet-9 121 65     SPACE admet-9 121 66 metabolism metabolism NOUN admet-9 121 67     SPACE admet-9 121 68 and and CCONJ admet-9 121 69     SPACE admet-9 121 70 pharmacokinetics pharmacokinetic NOUN admet-9 121 71     SPACE admet-9 121 72 pk pk NOUN admet-9 121 73                 SPACE admet-9 121 74 pharmacokinetics pharmacokinetic NOUN admet-9 121 75     SPACE admet-9 121 76 wan wan PROPN admet-9 121 77         SPACE admet-9 121 78 admet admet X admet-9 121 79     SPACE admet-9 121 80 & & CCONJ admet-9 121 81     SPACE admet-9 121 82 dmpk dmpk VERB admet-9 121 83     SPACE admet-9 121 84 1(3 1(3 NUM admet-9 121 85 ) ) PUNCT admet-9 121 86     SPACE admet-9 121 87 ( ( PUNCT admet-9 121 88 2013 2013 NUM admet-9 121 89 ) ) PUNCT admet-9 121 90     SPACE admet-9 121 91 19‐28 19‐28 NUM admet-9 121 92     SPACE admet-9 121 93 28 28 NUM admet-9 121 94         SPACE admet-9 121 95 cyp450 cyp450 NOUN admet-9 121 96             SPACE admet-9 121 97 cytochrome cytochrome NOUN admet-9 121 98     SPACE admet-9 121 99 p450 p450 NUM admet-9 121 100     SPACE admet-9 121 101 mdck mdck NOUN admet-9 121 102             SPACE admet-9 121 103 madin‐darby madin‐darby PROPN admet-9 121 104     SPACE admet-9 121 105 canine canine NOUN admet-9 121 106     SPACE admet-9 121 107 kidney kidney NOUN admet-9 121 108     SPACE admet-9 121 109 cells cell NOUN admet-9 121 110     SPACE admet-9 121 111 ppb ppb NOUN admet-9 121 112                 SPACE admet-9 121 113 plasma plasma NOUN admet-9 121 114     SPACE admet-9 121 115 protein protein NOUN admet-9 121 116     SPACE admet-9 121 117 binding bind VERB admet-9 121 118     SPACE admet-9 121 119 herg herg PROPN admet-9 121 120             SPACE admet-9 121 121 human human PROPN admet-9 121 122     SPACE admet-9 121 123 ether‐a‐go‐go ether‐a‐go‐go PROPN admet-9 121 124     SPACE admet-9 121 125 related relate VERB admet-9 121 126     SPACE admet-9 121 127 gene gene NOUN admet-9 121 128     SPACE admet-9 121 129 metid metid NOUN admet-9 121 130             SPACE admet-9 121 131 metabolite metabolite NOUN admet-9 121 132     SPACE admet-9 121 133 identification identification NOUN admet-9 121 134     SPACE admet-9 121 135 pd pd PROPN admet-9 121 136                 SPACE admet-9 121 137 pharmacodynamics pharmacodynamic NOUN admet-9 121 138     SPACE admet-9 121 139 p‐gp p‐gp NOUN admet-9 121 140               SPACE admet-9 121 141 p‐glycoprotein p‐glycoprotein NUM admet-9 121 142     SPACE admet-9 121 143 mtd mtd NOUN admet-9 121 144             SPACE admet-9 121 145 maximum maximum NOUN admet-9 121 146     SPACE admet-9 121 147 tolerated tolerate VERB admet-9 121 148     SPACE admet-9 121 149 dose dose NOUN admet-9 121 150     SPACE admet-9 121 151 ind ind NOUN admet-9 121 152                 SPACE admet-9 121 153 investigational investigational ADJ admet-9 121 154     SPACE admet-9 121 155 new new ADJ admet-9 121 156     SPACE admet-9 121 157 drug drug NOUN admet-9 121 158     SPACE admet-9 121 159 glp glp NOUN admet-9 121 160                 SPACE admet-9 121 161 good good ADJ admet-9 121 162     SPACE admet-9 121 163 lab lab NOUN admet-9 121 164     SPACE admet-9 121 165 practice practice NOUN admet-9 121 166     SPACE admet-9 121 167 cl cl NOUN admet-9 121 168                 SPACE admet-9 121 169 clearance clearance NOUN admet-9 121 170     SPACE admet-9 121 171 f f PROPN admet-9 121 172                 SPACE admet-9 121 173 absolute absolute ADJ admet-9 121 174     SPACE admet-9 121 175 bioavailability bioavailability NOUN admet-9 121 176     SPACE admet-9 121 177 ce(ss ce(ss PROPN admet-9 121 178 ) ) PUNCT admet-9 121 179             SPACE admet-9 121 180 effective effective ADJ admet-9 121 181     SPACE admet-9 121 182 plasma plasma NOUN admet-9 121 183     SPACE admet-9 121 184 concentration concentration NOUN admet-9 121 185     SPACE admet-9 121 186 at at ADP admet-9 121 187     SPACE admet-9 121 188 steady steady ADJ admet-9 121 189     SPACE admet-9 121 190 stage stage NOUN admet-9 121 191     SPACE admet-9 121 192 τ τ NOUN admet-9 121 193                 SPACE admet-9 121 194 dose dose NOUN admet-9 121 195     SPACE admet-9 121 196 interval interval NOUN admet-9 121 197     SPACE admet-9 121 198 cs cs PROPN admet-9 121 199                 SPACE admet-9 121 200 candidate candidate NOUN admet-9 121 201     SPACE admet-9 121 202 selection selection NOUN admet-9 121 203     SPACE admet-9 121 204 pmapa pmapa VERB admet-9 121 205             SPACE admet-9 121 206 parallel parallel ADJ admet-9 121 207     SPACE admet-9 121 208 artificial artificial ADJ admet-9 121 209     SPACE admet-9 121 210 membrane membrane NOUN admet-9 121 211     SPACE admet-9 121 212 permeability permeability NOUN admet-9 121 213     SPACE admet-9 121 214 assay assay VERB admet-9 121 215     SPACE admet-9 121 216 nmes nme NOUN admet-9 121 217             SPACE admet-9 121 218 new new ADJ admet-9 121 219     SPACE admet-9 121 220 molecular molecular ADJ admet-9 121 221     SPACE admet-9 121 222 entities entity NOUN admet-9 121 223             SPACE admet-9 121 224 © © PROPN admet-9 121 225 2013 2013 NUM admet-9 121 226     SPACE admet-9 121 227 by by ADP admet-9 121 228     SPACE admet-9 121 229 the the DET admet-9 121 230     SPACE admet-9 121 231 authors author NOUN admet-9 121 232 ; ; PUNCT admet-9 121 233     SPACE admet-9 121 234 licensee licensee NOUN admet-9 121 235     SPACE admet-9 121 236 iapc iapc PROPN admet-9 121 237 , , PUNCT admet-9 121 238     SPACE admet-9 121 239 zagreb zagreb PROPN admet-9 121 240 , , PUNCT admet-9 121 241     SPACE admet-9 121 242 croatia croatia PROPN admet-9 121 243 . . PUNCT admet-9 121 244     SPACE admet-9 122 1 this this DET admet-9 122 2     SPACE admet-9 122 3 article article NOUN admet-9 122 4     SPACE admet-9 122 5 is be AUX admet-9 122 6     SPACE admet-9 122 7 an an DET admet-9 122 8     SPACE admet-9 122 9 open‐access open‐access ADJ admet-9 122 10     SPACE admet-9 122 11 article article NOUN admet-9 122 12     SPACE admet-9 122 13 distributed distribute VERB admet-9 122 14     SPACE admet-9 122 15 under under ADP admet-9 122 16     SPACE admet-9 122 17 the the DET admet-9 122 18     SPACE admet-9 122 19 terms term NOUN admet-9 122 20     SPACE admet-9 122 21 and and CCONJ admet-9 122 22     SPACE admet-9 122 23 conditions condition NOUN admet-9 122 24     SPACE admet-9 122 25 of of ADP admet-9 122 26     SPACE admet-9 122 27 the the DET admet-9 122 28     SPACE admet-9 122 29 creative creative ADJ admet-9 122 30     SPACE admet-9 122 31 commons common NOUN admet-9 122 32     SPACE admet-9 122 33 attribution attribution NOUN admet-9 122 34     SPACE admet-9 122 35 license license NOUN admet-9 122 36     SPACE admet-9 122 37 ( ( PUNCT admet-9 122 38 http://creativecommons.org/licenses/by/3.0/ http://creativecommons.org/licenses/by/3.0/ PROPN admet-9 122 39 ) ) PUNCT admet-9 122 40                 SPACE