Percutaneous absorption and skin distribution of [14C]flutrimazole in mini-pigs.
The percutaneous absorption and skin distribution of a skin cream containing 1% 14C-labelled 1-[(fluorophenyl) (4-fluorophenyl) phenylmethyl]-1H-imidazole (flutrimazole, UR-4056, CAS 119006-77-8) was studied in minipigs. The same dose of flutrimazole was administered i.v. and topically (as a cream) on scarified skin according to a crossover protocol. Samples of urine and faeces were taken at various intervals after administration, and radioactivity was measured. The percentage of radioactivity accumulated in urine after topical and intravenous administration were 1.46% and 41.7%, respectively. In faeces, the percentage of radioactivity observed was 6.0% after intravenous administration, and none was detected after topical application. In order to study the distribution and penetration of [14C]flutrimazole, the cream was applied to intact and scarified skin. At various intervals after administration, skin samples were taken. The samples for the autoradiographic studies were cut transversely, and for the measurement of the levels of radioactivity at different skin depths, slices were cut parallel to the cutaneous layers. The results obtained indicate that [14C]flutrimazole penetrates quickly into the different epidermic layers and is retained mainly in the strata spinosum, granulosum and basale. The stratum basale possibly acts as a selective barrier preventing the penetration of the compound into the dermis. The percentage of radioactivity in the stratum corneum is lower than that detected in all the other epidermic layers taken together. The stratum corneum offers low resistance to penetration by the flutrimazole, which very probably crosses the epidermic strata by a transcellular route.
Conte
L
L
Research Centre, J. Uriach & Cía. S.A., Barcelona, Spain.
Ramis
J
J
Mis
R
R
Forn
J
J
Vilaró
S
S
Reina
M
M
Vilageliu
J
J
Basi
N
N
D000818:Animals; D000935:Antifungal Agents / Q000493:pharmacokinetics*; D001345:Autoradiography; D003022:Clotrimazole / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005243:Feces / Q000737:chemistry; D008297:Male; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D013552:Swine; D013556:Swine, Miniature
D000935:Antifungal Agents; C076986:flutrimazole; D003022:Clotrimazole