Antidermatophyte activity and PK/PD of ME1111 in a guinea pig model of tinea corporis.

ABSTRACT

Onychomycosis, a superficial fungal infection of the nails, is prevalent in many areas of the world. Topical agents for onychomycosis need to reach the subungual layer and nail bed to exert antifungal activity in the presence of keratin, the major component of the nail. It is difficult to evaluate the efficacy and pharmacodynamics of topical agents for onychomycosis in a non-clinical evaluation system. No consistent animal model has yet been established to predict the efficacy of topical agents for onychomycosis. In this study, we evaluated the pharmacokinetics and pharmacodynamics of ME1111 in a guinea pig model of tinea corporis designed to predict the efficacy of topical medication for onychomycosis in the vicinity of the nail bed. Trichophyton mentagrophytes TIMM1189 was infected on the back skin of guinea pigs, and ME1111 solution (5%, 10%, or 15%) was administered topically, once daily for 14 consecutive days. Following the completion of dosing, segments of skin from the site of infection were excised and cultured. The concentration of ME1111 in the back skin of guinea pigs increased with formulation concentration and correlated with mycological efficacy. We revealed the concentration required for ME1111 to be effective at the site of infection. Further analysis is needed to predict the efficacy of topical agents for onychomycosis by analyzing the relationship between PK/PD around the nail bed and factors such as subungual penetration and permeability.