Fall Clinical Dermatology Conference, Las Vegas, 20-23 October 2022

Brian Berman1 and Paul Tomondy2
1Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USA; 2Almirall LLC, Malvern, PA, USA.

• Cunningham et al1 compared the efficacy and tolerability of 5% 5-

fluorouracil (FU) cream + 0.005% calcipotriol ointment combination (FU+C)

with FU + vaseline combination (FU+V) treatment of actinic keratosis (AKs).

• The FU+V control resulted in 0% of participants having complete clearance

of face AKs and an unexpectedly low 4% of participants developing severe

erythema, possibly due to vaseline interfering with FU absorption.

• Mohney et al2 concluded that petrolatum + 5-FU is an inappropriate control

and no superiority claims from that study can be made vs topical FU.

• We report a 20-fold reduced penetration of FU in the presence of vaseline

(FU+V), and a 73% reduction in FU penetration in the presence of

calcipotriol ointment (FU+C).

• This is a mass balance study comparing marketed 5-FU alone (FU) and 1:1

weight combinations in vaseline (FU+V), 0.005% calcipotriol ointment

(FU+C) and vanicream (FU+vanicream).

• In vitro percutaneous absorption and penetration through dermatomed

human cadaver skin were assessed. After passing initial visual inspection,

barrier integrity of the skin tissue was evaluated using transepidermal

electrical resistance measurement. Skin permeation (5-6 specimens for

each test preparation) into receptor medium was studied at a clinically

relevant 8 hours.

Methods • Combining 5% 5-FU cream with vaseline interfered with the FU penetration
through skin, which was 20-fold lower with FU+V than with FU.

• This degree of reduction in penetration is greater than simply explained by

the lower final FU concentration in FU+V applied (2.5%).

• This markedly reduced penetration of FU in the presence of vaseline

(FU+V), taken with the 73% reduction in FU penetration in the presence of

calcipotriol ointment (FU+C), further point to the inappropriateness of using

a FU+V combination as a control for clinical studies and could lead to

erroneous superiority claims.

• BB received consulting honoraria from Almirall, Biofrontera, BMS, Pfizer, Evommune, Aiviva, Sirnaomics,

Pulse and Mediwound;

• PT is an Almirall USA employee.

Conflicts of interest

• 1Cunningham et al. J Clin Invest. 2017; 127:106-116.

• 2 Mohney et al. J Drugs Dermatol. 2022;21:60-65

References

Results

• At 8 hours, the mean (standard error of the mean) amount of FU penetrating

into the receptor medium was 6,440.2 (1,943.2) ng for FU alone, 316.2

(162.1) ng for FU+V, 1,727.7 (603.4) ng for FU+C and 1,734.6 (542.3) ng for

FU+vanicream (Fig. 1).

• The percentage release amount of FU in receptor at 8 hours was 1.1%,

1.7%, 1.3% and 5.0% and the percentage of FU in the total absorbed dose

was 10.1%, 9.2%, 7.3% and 18.7%, respectively (Fig. 2).

• The concentrations of FU in the receptor at 8 hours are shown in Fig. 3.

Figure 3. Mean 5-Fluorouracil Concentration in Total Absorbed Dose at 8h

Acknowledgements

0.7

399.9
681,0

996.3

316.2
244.3

602.0

1133.6

1727.7

450.3

945.5

1287.8

1734.6

1198.8

3672.6

4936.5

6440.2

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

6000

6500

0 1 2 3 4 5 6 7 8

M
e
a
n

 A
P

I 
(n

g
)

Time Point (hours)

FU+V

FU+C

FU+vanicream

FU

Figure 1. Mean Amount of 5-Fluorouracil in Receptor from 0 to 8h

Figure 2. Percentage Release Amount of 5-Fluorouracil in Receptor 

from 0 to 8h

API, active pharmaceutical ingredient; FU, 5% 5-FU cream alone; FU+V, FU+ 1:1 weight combinations in vaseline; FU+C, 

FU+ 1:1 weight combinations 0.005% calcipotriol ointment; FU-vanicream; FU+ 1:1 weight combinations vanicream

0.3%
0.5%

0.8%

1.1%

0.2%

0.6%

1.1%

1.7%

0.3%

0.7%
1.0%

1.3%

0.9%

2.8%

3.8%

5.0%

0%

1%

2%

3%

4%

5%

0 1 2 3 4 5 6 7 8

%
 R

e
le

a
s
e
 A

m
o

u
n

t 
o

f 
A

P
I

Time Point (hours)

FU+V

FU+C

FU+vanicream

FU

API, active pharmaceutical ingredient; FU, 5% 5-FU cream alone; FU+V, FU+ 1:1 weight combinations in vaseline; FU+C, 

FU+ 1:1 weight combinations 0.005% calcipotriol ointment; FU-vanicream; FU+ 1:1 weight combinations vanicream

Results

API, active pharmaceutical ingredient; FU, 5% 5-FU cream alone; FU+V, FU+ 1:1 weight combinations in vaseline; FU+C, 

FU+ 1:1 weight combinations 0.005% calcipotriol ointment; FU-vanicream; FU+ 1:1 weight combinations vanicream

• Writing assistance provided by TFS HealthScience.

• This study was funded by Almirall.

105.4

595.9 578.2

2,146.7

0

500

1000

1500

2000

2500

FU+V FU+C FU+vanicream FU

M
e
a
n

 A
P

I 
(n

g
/m

L
)

• To compare the skin absorption/penetration of 4 different 5% 5-FU

formulations, including FU+V.

Synopsis

Objective

Conclusions

Human Skin Absorption and Penetration Study of Four Different Topical Formulations of 5-Fluorouracil                   


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