Pharmacokinetics of terbinafine in the nail

Abstract

Information on the pharmacokinetics of terbinafine (Lamisil®) in the nail is essential for the rational planning of optimal therapeutic regimens. There are important inherent difficulties in delivering drugs in appropriate concentrations to diseased areas of the nail that are related to biochemical and physical properties of the nail plate. Whereas the inflammatory response and stratum corneum disruption in skin diseases may make it easier for drugs to reach their target, in disease of the nail plate, the crumbling and resultant lack of contiguity may add to the problems of drug penetration. Several clinical studies of terbinafine in onychomycosis have suggested that, because of its fungicidal properties, short courses of therapy can be effective. In a recent study in Cardiff, the levels of terbinafine in individual distal nail clippings were measured in 12 patients taking 250 mg of oral terbinafine daily for up to 48 weeks. Terbinafine was detected at a mean time of approximately 8 weeks, but as early as 3 weeks in one patient, confirming that terbinafine diffuses rapidly through nail. In another recent Cardiff study aimed at measuring the relationship of oral doses of terbinafine to both proximal and distal nail plate drug levels, and its persistence following cessation of therapy, the results appear to support the effectiveness of short-course terbinafine therapy. Nail pharmacokinetic data are still required to guide the optimal management of relapsers and slow responders, and nail drug levels as a clinical investigation may prove helpful in the management of some patients.