Pharmacokinetics of terbinafine in the nail

Oral terbinafine is an effective therapy for dermatophyte onychomycosis, presumably because it reaches the infected areas of the nail rapidly and in fungicidal concentrations. For planning optimal clinical dosage regimes, it is necessary to know the rate of terbinafine movement through the nail plate, the concentrations achieved, and the persistence in the nail plate after stopping treatment. In a study of 12 patients receiving terbinafine at 250 mg/day for up to 48 weeks, measurement of terbinafine in distal nail clippings demonstrated that the drug was first detectable 3-18 weeks after starting therapy. A level of 0.25-0.55 ng/mg was quickly achieved and remained stable. Concentrations of terbinafine in distal clippings of unaffected nails were similar to those in affected nails. Although the average nail concentrations are within the fungicidal range for dermatophytes, the anatomy of an infected nail may result in relatively protected areas of infection. This results in the occasional persistence or recurrence of dermatophytic infection observed in some cases. However, the results of this study justify further trials of 'short-term' oral terbinafine therapy for onychomycosis. A current study is addressing the relationship of oral dosage to nail drug concentration and its later persistence in the nail plate.