UNLABELLED: The effects of oral administration of sertraline on the plasma concentration profile and renal clearance of digoxin were assessed in 20 healthy male subjects in a double-blind, randomized study. METHOD: All subjects first received digoxin 0.5 mg twice daily on Day 1, 0.25 mg twice daily on Day 2, and 0.25 mg daily thereafter. On Day 11, 10 subjects began concomitant sertraline administration with an initial dose of 50 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 received concomitant digoxin and placebo for 17 days beginning on Day 11. Trough plasma concentrations of digoxin were monitored daily beginning on Day 7. Blood samples and 24-hour urine collections were used to determine steady-state digoxin concentration and renal clearance before, during, and after sertraline coadministration. RESULTS:Sertraline had no effect on digoxin pharmacokinetics, except for a decrease in the time to reach the maximum plasma digoxin concentration (Tmax) compared with placebo (p = .0046), a finding thought to be of limited clinical significance. Side effects of mild-to-moderate severity were reported by 5 of 10 sertraline-treated subjects and by 6 of 10 placebo-treated subjects. CONCLUSION: The results of this study suggest that dosing adjustments of digoxin may not be necessary in patients receiving concomitant sertraline administration.
RCT Entities:
UNLABELLED: The effects of oral administration of sertraline on the plasma concentration profile and renal clearance of digoxin were assessed in 20 healthy male subjects in a double-blind, randomized study. METHOD: All subjects first received digoxin 0.5 mg twice daily on Day 1, 0.25 mg twice daily on Day 2, and 0.25 mg daily thereafter. On Day 11, 10 subjects began concomitant sertraline administration with an initial dose of 50 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 received concomitant digoxin and placebo for 17 days beginning on Day 11. Trough plasma concentrations of digoxin were monitored daily beginning on Day 7. Blood samples and 24-hour urine collections were used to determine steady-state digoxin concentration and renal clearance before, during, and after sertraline coadministration. RESULTS:Sertraline had no effect on digoxin pharmacokinetics, except for a decrease in the time to reach the maximum plasma digoxin concentration (Tmax) compared with placebo (p = .0046), a finding thought to be of limited clinical significance. Side effects of mild-to-moderate severity were reported by 5 of 10 sertraline-treated subjects and by 6 of 10 placebo-treated subjects. CONCLUSION: The results of this study suggest that dosing adjustments of digoxin may not be necessary in patients receiving concomitant sertraline administration.
Authors: David N Juurlink; Muhammad M Mamdani; Alexander Kopp; Nathan Herrmann; Andreas Laupacis Journal: Br J Clin Pharmacol Date: 2005-01 Impact factor: 4.335
Authors: Harma Ellens; Shibing Deng; Joann Coleman; Joe Bentz; Mitchell E Taub; Isabelle Ragueneau-Majlessi; Sophie P Chung; Krisztina Herédi-Szabó; Sibylle Neuhoff; Johan Palm; Praveen Balimane; Lei Zhang; Masoud Jamei; Imad Hanna; Michael O'Connor; Dallas Bednarczyk; Malin Forsgard; Xiaoyan Chu; Christoph Funk; Ailan Guo; Kathleen M Hillgren; Libin Li; Anne Y Pak; Elke S Perloff; Ganesh Rajaraman; Laurent Salphati; Jan-Shiang Taur; Dietmar Weitz; Heleen M Wortelboer; Cindy Q Xia; Guangqing Xiao; Tetsuo Yamagata; Caroline A Lee Journal: Drug Metab Dispos Date: 2013-04-25 Impact factor: 3.922