Absence of a sertraline-mediated effect on digoxin pharmacokinetics and electrocardiographic findings.
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.


METHODS
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.


CONCLUSIONS
The results of this study suggest that dosing adjustments of digoxin may not be necessary in patients receiving concomitant sertraline administration.
Rapeport
W G
WG
Pfizer Central Research, Sandwich, Kent, United Kingdom.
Coates
P E
PE
Dewland
P M
PM
Forster
P L
PL
D015057:1-Naphthylamine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D000284:Administration, Oral; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D016001:Confidence Intervals; D004077:Digoxin / Q000037:antagonists & inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004347:Drug Interactions; D004562:Electrocardiography / Q000187:drug effects*; D006801:Humans; D008297:Male; D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D020280:Sertraline
D015057:1-Naphthylamine; D004077:Digoxin; D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline