Pharmacokinetic interaction between zolpidem and carbamazepine in healthy volunteers

J Clin Pharmacol. 2011 Aug;51(8):1233-6. doi: 10.1177/0091270010383690. Epub 2010 Nov 22.

Abstract

The objective of this study was to evaluate the pharmacokinetic interaction between zolpidem and carbamazepine in healthy volunteers. The study consisted of 2 periods: period 1 (reference), when each volunteer received a single dose of 5 mg zolpidem, and period 2 (test), when each volunteer received a single dose of 5 mg zolpidem and 400 mg carbamazepine. Between the 2 periods, the participants were treated for 15 days with a single daily dose of 400 mg carbamazepine. Pharmacokinetic parameters of zolpidem administered in each treatment period were calculated using noncompartmental analysis. In the 2 periods of treatments, the mean peak plasma concentrations (C(max)) were 59 ng/mL (zolpidem alone) and 35 ng/mL (zolpidem after pretreatment with carbamazepine). The t(max), times taken to reach C(max), were 0.9 hours and 1.0 hour, respectively, and the total areas under the curve (AUC(0-∞)) were 234.9 ng·h/mL and 101.5 ng·h/mL, respectively. The half-life of zolpidem was 2.3 and 1.6 hours, respectively. Carbamazepine interacts with zolpidem in healthy volunteers and lowers its bioavailability by about 57%. The experimental data demonstrate the pharmacokinetic interaction between zolpidem and carbamazepine and suggest that the observed interaction may be clinically significant, but its relevance has to be confirmed.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anticonvulsants / pharmacology*
  • Biological Availability
  • Carbamazepine / pharmacology*
  • Cross-Over Studies
  • Cytochrome P-450 Enzyme System / biosynthesis
  • Drug Interactions
  • Enzyme Induction / drug effects
  • GABA-A Receptor Agonists / blood
  • GABA-A Receptor Agonists / pharmacokinetics*
  • Half-Life
  • Humans
  • Hypnotics and Sedatives / blood
  • Hypnotics and Sedatives / pharmacokinetics*
  • Male
  • Metabolic Clearance Rate
  • Pyridines / blood
  • Pyridines / pharmacokinetics*
  • Young Adult
  • Zolpidem

Substances

  • Anticonvulsants
  • GABA-A Receptor Agonists
  • Hypnotics and Sedatives
  • Pyridines
  • Carbamazepine
  • Zolpidem
  • Cytochrome P-450 Enzyme System