NAIL INCORPORATION KINETICS OF TERBINAFINE IN ONYCHOMYCOSIS PATIENTS

Patients with toe-nail onychomycosis were treated with terbinafine (25 0 mg daily, n = 20) for either 6 or 12 weeks in a randomized double-bl ind study. Plasma and distal nail clippings were taken before initiati on of therapy and 1, 6, 12, 18, 21, 36 and 48 weeks thereafter. Analyt ical data of terbinafine extracted from nail clippings or plasma were obtained by high-performance liquid chromatography (HPLC). Nail extrac ts and isolated HPLC terbinafine peaks were analysed using a combined gas chromatography-mass spectroscopy system (GC-MS) for unequivocal id entification of the drug. Terbinafine could be detected in the distal nail in the majority of the patients within 1 week of starting therapy . Maximum terbinafine levels of 0.52 and 1.01 mu g/g were measured aft er 18 weeks in the 6- and 12-week treatment groups, respectively. Whil e plasma levels decreased rapidly after termination of therapy terbina fine was detected in the nails as long as 30 weeks (6 weeks treatment) and 36 weeks (12 weeks treatment) after termination of therapy at a r ange of 0.28-0.19 mu g/g. The drug concentrations measured at all time points are well above the minimum inhibitory concentration (MIG) for dermatophytes and other fungi. These data suggest that the drug reache s the nail plate rapidly and persists there for several months after c essation of active treatment.