ABSENCE OF A SERTRALINE-MEDIATED EFFECT ON DIGOXIN PHARMACOKINETICS AND ELECTROCARDIOGRAPHIC FINDINGS

The effects of oral administration of sertraline on the plasma concent ration profile and renal clearance of digoxin were assessed in 20 heal thy male subjects in a double-blind, randomized study. Method: All sub jects first received digoxin 0.5 mg twice daily on Day 1, 0.25 mg twic e daily on Day 2, and 0.25 mg daily thereafter. On Day 11, 10 subjects began concomitant sertraline administration with an initial dose of 5 0 mg/day that was titrated upward over 7 days to 200 mg/day, which was given over the remainder of the study period. The other 10 subjects r eceived concomitant digoxin and placebo for 17 days beginning on Day 1 1. Trough plasma concentrations of digoxin were monitored daily beginn ing on Day 7. Blood samples and 24-hour urine collections were used to determine steady-state digoxin concentration and renal clearance befo re, during, and after sertraline coadministration. Results: Sertraline had no effect on digoxin pharmacokinetics, except for a decrease in t he time to reach the maximum plasma digoxin concentration (T-max) comp ared with placebo (p = .0046), a finding thought to be of limited clin ical significance. Side effects of mild-to-moderate severity were repo rted by 5 of 10 sertraline-treated subjects and by 6 of 10 placebo-tre ated subjects. Conclusion: The results of this study suggest that dosi ng adjustments of digoxin may not be necessary in patients receiving c oncomitant sertraline administration.