title: Absence of a sertraline-mediated effect on the pharmacokinetics and pharmacodynamics of carbamazepine.
abstract: A double-blind, randomized, placebo-controlled study was conducted in 14 healthy male volunteers to assess the effects of sertraline on the pharmacokinetics and pharmacodynamics of carbamazepine.
  
  
  METHODS
  Subjects received carbamazepine 200 mg once daily for 2 days and every 12 hours thereafter. On Days 16 to 32, subjects also received either sertraline or placebo daily. The dose of sertraline was increased from 50 to 200 mg daily over 7 days; the 200-mg dose was given for 10 days. Samples for pharmacokinetic analyses were obtained on Days 15 and 32; trough plasma concentrations of carbamazepine and its principal metabolite, carbamazepine-10, 11-epoxide (CBZ-E), were determined daily beginning on Day 13. Cognitive function testing was performed on Day 1 before carbamazepine dosing (baseline), Day 15 (carbamazepine alone), and Day 32 (carbamazepine plus sertraline or placebo).
  
  
  RESULTS
  There were no significant differences between the sertraline and placebo groups in any of the pharmacokinetic parameters for carbamazepine or CBZ-E. Carbamazepine alone impaired cognitive function. The addition of sertraline did not potentiate these effects. Side effects were reported by 2 subjects in each group, but none were severe.
  
  
  CONCLUSIONS
  These findings indicate that sertraline does not affect the pharmacokinetics of carbamazepine or its principal metabolite and does not potentiate the cognitive effects of carbamazepine.
authors.affiliation: Pfizer Central Research, Sandwich, Kent, United Kingdom.
authors.forename: W G
authors.initials: WG
authors.lastname: Rapeport
authors.forename: S A
authors.initials: SA
authors.lastname: Williams
authors.forename: D C
authors.initials: DC
authors.lastname: Muirhead
authors.forename: P M
authors.initials: PM
authors.lastname: Dewland
authors.forename: T
authors.initials: T
authors.lastname: Tanner
authors.forename: K
authors.initials: K
authors.lastname: Wesnes
mesh_terms: D015057:1-Naphthylamine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D000328:Adult; D002220:Carbamazepine / Q000097:blood / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D004347:Drug Interactions; D006801:Humans; D008297:Male; D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D020280:Sertraline
chemical_list: D015057:1-Naphthylamine; D002220:Carbamazepine; D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline