EVALUATION OF EFFECTS OF TERBINAFINE ON SINGLE ORAL DOSE PHARMACOKINETICS AND ANTICOAGULANT ACTIONS OF WARFARIN IN HEALTHY-VOLUNTEERS

Study Objective. To evaluate the potential effects of oral terbinafine , a new synthetic antifungal agent of the allylamine class, on the pha rmacokinetics and pharmacodynamics of racemic warfarin. Design. Random ized, double-blind, placebo-controlled, crossover study. Subjects. Six teen healthy men. Interventions. Placebo or terbinafine 250 mg was adm inistered once/day for 14 consecutive days, separated by a washout per iod lasting at least 2 weeks. A single oral dose of racemic warfarin 3 0 mg was coadministered with placebo or terbinafine on day 8 of each t reatment period. Blood samples were collected for 168 hours after admi nistration of warfarin to determine the drug's pharmacokinetics and an ticoagulant effects. Measurements and Main Results. No major differenc es were seen in the plasma concentration-time profiles of a single dos e of warfarin administered with terbinafine or with placebo. Conclusio ns. Because of the lack of clinically significant interactions between terbinafine and warfarin during multiple-dose administration of terbi nafine, no adjustment of warfarin dosage during concomitant therapy ap pears to be necessary.