Penetration of tinidazole into skin blister fluid following its oral administration.

Abstract

Plasma and skin blister fluid concentrations of tinidazole following a single oral dose of 2 g drug, and after multiple doses of 0.25 g every 12 h, were determined. Skin blisters were produced by direct application of 0.25% cantharidin ointment to the skin. The maximum concentration in plasma of about 36 mg.l-1 was observed after about 2 h, whereas in skin blister fluid the peak occurred after about 6 h and was 30 mg.l-1. The half-life in plasma was slightly shorter than in blister fluid at 17 and 19 h, respectively, but the difference was not significant. The penetration of tinidazole into cantharidin-induced skin blister fluid, defined according to Wise as the ratio of the AUCs in blister fluid and plasma was 1.00. During routine treatment with tinidazole (0.25 g every 12 h), the concentrations in plasma and blister fluid collected before and 3 h after the morning dose exceeded the minimal inhibitory concentrations for susceptible pathogens. The results provide a pharmacokinetic basis for the proven efficacy of tinidazole in the treatment of protozoal and anaerobic infections.