Effect of voriconazole on the pharmacokinetics and pharmacodynamics of zolpidem in healthy subjects

Br J Clin Pharmacol. 2007 Jan;63(1):116-20. doi: 10.1111/j.1365-2125.2006.02707.x. Epub 2006 Jul 6.

Abstract

Aims: To assess the effect of voriconazole on the pharmacokinetics and pharmacodynamics of zolpidem.

Methods: In a randomized cross-over study with two phases, 10 healthy subjects ingested 10 mg of zolpidem with or without oral voriconazole pretreatment. The concentrations of zolpidem were measured in plasma up to 24 h and pharmacodynamic variables were monitored for 12 h.

Results: Voriconazole increased the peak plasma concentration of zolpidem by 1.23-fold [P < 0.05; 90% confidence interval (CI) 1.05, 1.45] and the area under the plasma zolpidem concentration-time curve by 1.48-fold (P < 0.001; 90% CI 1.29, 1.74). The time to peak plasma zolpidem concentration was unchanged by voriconazole but the half-life was prolonged from 3.2 to 4.1 h (P < 0.01; 95% CI on the difference 0.27, 1.45). The pharmacodynamics of zolpidem were unaffected by voriconazole.

Conclusion: Voriconazole caused a moderate increase in exposure to zolpidem in healthy young subjects but no clear pharmacodynamic changes were observed between the groups.

Publication types

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

MeSH terms

  • Adult
  • Antifungal Agents / pharmacology*
  • Cross-Over Studies
  • Drug Interactions
  • Humans
  • Hypnotics and Sedatives / pharmacokinetics*
  • Male
  • Pyridines / pharmacokinetics*
  • Pyrimidines / pharmacology*
  • Triazoles / pharmacology*
  • Voriconazole
  • Zolpidem

Substances

  • Antifungal Agents
  • Hypnotics and Sedatives
  • Pyridines
  • Pyrimidines
  • Triazoles
  • Zolpidem
  • Voriconazole