A comparison of the skin permeation of three topical 0.5% fluorouracil formulations with that of a 5% formulation.
BACKGROUND
Topical fluorouracil has proven efficacy in the treatment of actinic keratosis. The systemic absorption of various topical formulations of fluorouracil varies, however, and may be affected by the concentration and delivery system used.


OBJECTIVE
This study compared the flux and percutaneous absorption of 3H-labeled fluorouracil from three 0.5% fluorouracil formulations incorporated into a porous microsphere delivery system with those from a commercially available 5% fluorouracil formulation.


METHODS
Penetration of all formulations through the skin was sampled every 3 hours for 24 hours using full-thickness human cadaver skin samples mounted in a Bronaugh flow-through diffusion cell apparatus. Total absorption was defined as the sum of the amount of cumulative flux through the skin over 24 hours and the amount retained in the skin at 24 hours.


RESULTS
The flux through the skin of the 5% fluorouracil formulation was 20 to 40 times greater (normalized, 2-4 times greater) than that of the 0.5% fluorouracil formulations. A higher percentage of absorbed fluorouracil was retained in the skin after 24 hours with the 0.5% formulations (86%-92%) than with the 5% formulation (54%).


CONCLUSIONS
These findings suggest that the 0.5% formulations are associated with less flux through the skin than the 5% formulation and, therefore, potentially less systemic exposure.
Levy
S
S
Dermik Laboratories Inc. Berwyn, Pennsylvania 19312, USA. Sharon.Levy@Aventis.com
Furst
K
K
Chern
W
W
D000287:Administration, Topical; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D005472:Fluorouracil / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D008863:Microspheres; D009824:Ointments; D012869:Skin Absorption
D000964:Antimetabolites, Antineoplastic; D009824:Ointments; D005472:Fluorouracil