EFFECTS OF TERBINAFINE ON THE PHARMACOKINETICS OF DIGOXIN IN HEALTHY-VOLUNTEERS

Study Objective. To assess the potential effects of terbinafine, a new synthetic allylamine antifungal agent, on the pharmacokinetics of a s ingle 0.75-mg oral dose of digoxin. Design. Randomized, double-blind, placebo-controlled, crossover study consisting of two treatment period s. Subjects. Sixteen healthy men and women volunteers. Interventions. During treatment A, placebo was administered once/day for 12 days; dur ing treatment B, terbinafine 250 mg was administered orally once/day f or 12 days. The washout period between treatments was at least 2 weeks . A single 0.75-mg oral dose of digoxin was administered on day 8 of e ach period. Blood samples were collected after administration of digox in to determine pharmacokinetics. Measurements and Main Results. Compa red with placebo, terbinafine did not alter the time course of the dig oxin serum levels. Although the time to maximum peak concentration wit h terbinafine was slightly reduced, the maximum concentration and area under the serum drug concentration-time curve from time zero to 120 h ours were not significantly different with terbinafine than with place bo. No drug-related side effects were reported with either active trea tment, and no clinically significant changes in vital signs, physical examination results, electrocardiograms, or clinical laboratory result s were observed. Conclusions. No special dosage adjustments for digoxi n appear to be necessary during concomitant therapy with terbinafine.