Levels of terbinafine in plasma, stratum corneum, dermis-epidermis (without stratum corneum), sebum, hair and nails during and after 250 mg terbinafine orally once per day for four weeks

Abstract

The distribution of terbinafine in stratum corneum dermis-epidermis (without stratum corneum), sebum, hair, nails and plasma was studied in human male volunteers during and after 250 mg orally once daily for 28 days. The highest concentration was seen in sebum, 56.07 μg/g, after 14 days of therapy. The concentration was still 1.0 μg/g 44 days after stop of medication. In stratum corneum the highest concentration, 14.4 μg/g, was seen 1 day after the last day of therapy, and it was 2.1 μg/g 44 days after stop of medication. The concentrations in hair and nails were lower with a maximum of 2.36 and 0.39 μg/g respectively, 1 day after stop of therapy, and still 0.21 μg/g in hair and 0.09 μg/g in nails 55 days after the last day of medication. With the exception of nails, all other tissue levels were at all times above the plasma concentrations. For nails, tissue levels exceeded that of plasma as early as 1 day after stop of medication, and this difference continued to increase until the last day of tissue sampling, 55 days after the last tablet. These results indicate that terbinafine is delivered to the stratum corneum through sebum and to a minor extent by direct diffusion through dermis-epidermis. Probably short-term therapy with terbinafine may be effective in the treatment of several dermatomycoses, due to the strong binding of terbinafine to stratum corneum for a long time after stop of medication. Details of skin distribution of orally active antifungal agents should provide the basis for a more rational, pharmacodynamic-oriented approach to antifungal therapy than the use of traditional blood levels.