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

Abstract

We examined anti-Trichophyton mentagrophytes activity, cutaneous penetration, and skin localization of mentagrophytes KD-04 were 0.025 and 0.39 ag/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 ,ig 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.

In Vitro Antifungal Activity of KP-103, a Novel Triazole Derivative, and Its Therapeutic Efficacy against Experimental Plantar Tinea Pedis and Cutaneous Candidiasis in Guinea Pigs

“…It has been reported that various antifungal agents developed recently, including neticonazole, lanoconazole, butenafine, amorolfine, and terbinafine, exhibit prolonged cutaneous retention times (2,7,25,29,33) and achieve concentrations far above the MICs for most dermatophytes in the horny layer when they are applied to the skin (5,22,34). However, it looks likely that these antifungal agents mostly exist in an inactive form in the skin tissues because several studies have demonstrated that their in vitro activities were markedly lower in the presence of keratin (1,21,30) or serum (6,8,14), probably through drug-protein interactions.…”

“…In recent years, an imidazole (lanoconazole) (20) and three classes of antifungal compounds, a benzylamine (butenafine) (17), an allylamine (terbinafine) (27), and a morpholine (amorolfine) (32), have been successfully developed and introduced into clinical use. These newer drugs are more highly active than the former imidazoles against dermatophytes in vitro (17,20,27,32) and in vivo in guinea pig models of dermatophytosis (2,3,4,5,25,26,29,38).…”

“…Therefore, when antifungal agents are topically applied to the skin, therapeutic efficacy depends not only on their antifungal activities but also on their pharmacokinetic properties in skin tissue (31,34). Several antifungal drugs such as lanoconazole (22), terbinafine (34), and butenafine (5) have been demonstrated to accumulate well in the horny layer when they are applied topically. However, almost all of these drugs appear to be inactivated in the horny layer because it was shown by in vitro experiments that they are strongly bound to keratin, with a resultant loss of the activity (1,21; Y. Tatsumi, M. Yokoo, T. Arika, H. Ogura, K. Nagai, T. Naito, and H. Yamaguchi, Abstr.…”

Therapeutic Efficacy of Topically Applied KP-103 against Experimental Tinea Unguium in Guinea Pigs in Comparison with Amorolfine and Terbinafine

“…Antifungal drugs such as lanoconazole, butenafine, terbinafine, and amorolfine developed in recent years have potent in vitro antidermatophyte activity (11,14,18,28) in the horny layer and nails at high levels when topically applied (1,15,19,29). In our previous study with a guinea pig tinea pedis model (26), we demonstrated that the therapeutic efficacy of lanoconazole was not correctly assessed by the conventional culture method because of a carryover of the drug remaining in the treated skin tissues to the culture media for detecting fungi.…”

“…KP-103, amorolfine, or terbinafine was dissolved in a mixture of polyethylene glycol 400-ethanol (75:25, vol/vol) (1,17,(24)(25)(26) at 1% for topical application. Terbinafine hydrochloride tablets (Lamisil) were purchased from Novartis Pharma KK and suspended in coconut oil with a mortar, and the suspension was dispensed into capsules for oral administration.…”