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We examined anti-Trichophyton mentagrophytes activity, cutaneous penetration, and skin localization of butenafine, a novel benzylamine antifungal agent. The following results were obtained. (i) In the guinea pig dorsal skin trichophytosis model, butenafine produced complete eradication of fungi from infected sites. Clotrimazole was active when animals were infected with 10(4) or 10(5) cells but was almost inactive when the inoculum size was 10(6) cells. (ii) The MICs of butenafine and clotrimazole against arthrospores of T. mentagrophytes KD-04 were 0.025 and 0.39 microgram/ml, respectively. (iii) When 0.2 ml of a 1% 14C-butenafine solution was applied for 23 h/day for 7 days, high radioactivity corresponding to 250 to 500 micrograms of butenafine per g of skin in the epidermis, including the horny layer, was observed. (iv) Butenafine penetrates through transepidermal and transfollicular routes. The excellent therapeutic efficacy of butenafine on experimental dermatophytosis may be attributed to its low MIC and good penetration and distribution in the horny layer and hair follicles, where fungi reside.

Anti-Trichophyton mentagrophytes activity and percutaneous permeation of butenafine in guinea pigs