Terbinafine levels in serum, stratum corneum, dermis-epidermis (without stratum corneum), hair, sebum and eccrine sweat

Abstract

We determined terbinafine levels in serum, stratum corneum, dermis-epidermis (without stratum corneum), hair, sebum and eccrine sweat before, during and after 250 mg doses orally to volunteers once daily. Terbinafine is concentrated rapidly in stratum corneum (up to 9.1 micrograms/g of tissue) primarily by diffusion from the vascular system through the dermisepidermis. It also reaches high concentration in sebum (up to 45.1 micrograms/ml) after several days and continue to concentrate in sebum for up to two days after discontinuation of drug. Hair concentration reach levels of 2.6 micrograms/g of tissue indicating high drug levels in and around the hair follicle. It is not found in sweat. Plasma levels range between 0.1 and 1.0 micrograms/ml. There is a tenfold accumulation of drug in stratum corneum by day 2. Elimination of drug from tissue occurs with a half-life of 4 to 5 days and with the potential for drug levels above fungicidal concentrations for dermatophytes for more than 3 weeks. The tissue pharmacokinetic profile of terbinafine is similar to that of another lipophilic drug, itraconazole, but is very different from ketoconazole and griseofulvin. Higher levels of terbinafine are achieved than of either of the imidazoles and remain longer than griseofulvin.