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 single 0.75-mg oral dose of digoxin.

DESIGN

Randomized, double-blind, placebo-controlled, crossover study consisting of two treatment periods.

SUBJECTS

Sixteen healthy men and women volunteers.

INTERVENTIONS

During treatment A, placebo was administered once/day for 12 days; during treatment B, terbinafine 250 mg was administered orally once/day for 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 each period. Blood samples were collected after administration of digoxin to determine pharmacokinetics.

MEASUREMENTS AND MAIN RESULTS

Compared with placebo, terbinafine did not alter the time course of the digoxin serum levels. Although the time to maximum peak concentration with terbinafine was slightly reduced, the maximum concentration and area under the serum drug concentration-time curve from time zero to 120 hours were not significantly different with terbinafine than with placebo. No drug-related side effects were reported with either active treatment, and no clinically significant changes in vital signs, physical examination results, electrocardiograms, or clinical laboratory results were observed.

CONCLUSIONS

No special dosage adjustments for digoxin appear to be necessary during concomitant therapy with terbinafine.