Stratum corneum pharmaco­kinetics of the anti-fungal drug, terbinafine, in a novel topical formulation, for single-dose application in dermatophytoses

ABSTRACT Objective: The stratum corneum (SC) pharmacokinetics of terbinafine following single-dose administration of a novel cutaneous solution (film-forming solution, FFS) containing terbinafine hydrochloride and a film-forming agent, was investigated in three studies. Terbinafine 1% cream (Lamisil†) was included as a benchmark in two of these studies. Research design and methods: Drugs were applied to areas of the back, and skin strips were taken from defined areas at baseline and from 1 to 312 h after application. Samples were analysed using validated liquid chromatography/mass spectrometry. Results: The residence time of the film on the skin was up to 72 h after application (up to 12 h for the 1% cream). After application of terbinafine FFS, 30% of the total amount of drug delivered into the SC occurred during the first 2 h, 31% from 2–12 h, and 39% thereafter. The Cmax was observed as early as 1.5 h (tmax). SC levels were still detected after 13 days (24 ng/cm2) (t½ was 162 h). Terbinafine 1% cream showed a similar tmax (2 h) with a lower Cmax than terbinafine 1% FFS, and mean SC levels after 7 days of treatment were 46 ng/cm2 (day 13). The t½ was 68 h. Washing at 30 min removed 86% of the film still present on the surface; the decrease of terbinafine concentration in the SC was 84%. A later washing at 12 h removed 73% of the film in comparison to non-washed skin and induced a decrease in the terbinafine content in the SC of 27%. Conclusions: The SC pharmacokinetic profile of terbinafine 1% FFS indicates that this novel formulation is efficient in delivering high amounts of terbinafine to the skin for a prolonged time and supports its use in the treatment of dermatophytoses with a single application. Introduction