Evaluation of effects of terbinafine on single oral dose pharmacokinetics and anticoagulant actions of warfarin in healthy volunteers.

Author(s): Guerret M, Francheteau P, Hubert M

Affiliation(s): Development Department, Novartis Pharmaceuticals, Rueil-Malmaison, France.

Publication date & source: 1997-07, Pharmacotherapy., 17(4):767-73.

Publication type: Clinical Trial; Randomized Controlled Trial

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.