Effects of terbinafine on the pharmacokinetics of digoxin in healthy volunteers.
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.


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


METHODS
Sixteen healthy men and women volunteers.


METHODS
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.


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.
Tarral
A
A
Development Department, Novartis Pharmaceuticals, Rueil-Malmaison, France.
Francheteau
P
P
Guerret
M
M
D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000493:pharmacokinetics*; D000935:Antifungal Agents / Q000494:pharmacology*; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D004077:Digoxin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D009281:Naphthalenes / Q000008:administration & dosage / Q000494:pharmacology*; D000077291:Terbinafine
D000889:Anti-Arrhythmia Agents; D000935:Antifungal Agents; D009281:Naphthalenes; D004077:Digoxin; D000077291:Terbinafine