STUDY OBJECTIVE: To evaluate the potential effects of oral terbinafine, a new synthetic antifungal agent of the allylamine class, on the pharmacokinetics and pharmacodynamics of racemic warfarin. DESIGN: Randomized, double-blind, placebo-controlled, crossover study. SUBJECTS:Sixteen healthy men. INTERVENTIONS:Placebo or terbinafine 250 mg was administered once/day for 14 consecutive days, separated by a washout period lasting at least 2 weeks. A single oral dose of racemic warfarin 30 mg was coadministered with placebo or terbinafine on day 8 of each treatment period. Blood samples were collected for 168 hours after administration of warfarin to determine the drug's pharmacokinetics and anticoagulant effects. MEASUREMENTS AND MAIN RESULTS: No major differences were seen in the plasma concentration-time profiles of a single dose of warfarin administered with terbinafine or with placebo. CONCLUSIONS: Because of the lack of clinically significant interactions between terbinafine and warfarin during multiple-dose administration of terbinafine, no adjustment of warfarin dosage during concomitant therapy appears to be necessary.
RCT Entities:
STUDY OBJECTIVE: To evaluate the potential effects of oral terbinafine, a new synthetic antifungal agent of the allylamine class, on the pharmacokinetics and pharmacodynamics of racemic warfarin. DESIGN: Randomized, double-blind, placebo-controlled, crossover study. SUBJECTS: Sixteen healthy men. INTERVENTIONS: Placebo or terbinafine 250 mg was administered once/day for 14 consecutive days, separated by a washout period lasting at least 2 weeks. A single oral dose of racemic warfarin 30 mg was coadministered with placebo or terbinafine on day 8 of each treatment period. Blood samples were collected for 168 hours after administration of warfarin to determine the drug's pharmacokinetics and anticoagulant effects. MEASUREMENTS AND MAIN RESULTS: No major differences were seen in the plasma concentration-time profiles of a single dose of warfarin administered with terbinafine or with placebo. CONCLUSIONS: Because of the lack of clinically significant interactions between terbinafine and warfarin during multiple-dose administration of terbinafine, no adjustment of warfarin dosage during concomitant therapy appears to be necessary.
Authors: Nina Isoherranen; Justin D Lutz; Sophie P Chung; Houda Hachad; Rene H Levy; Isabelle Ragueneau-Majlessi Journal: Chem Res Toxicol Date: 2012-09-27 Impact factor: 3.739