Effect of efavirenz on the pharmacokinetics of ketoconazole in HIV-infected patients

Eur J Clin Pharmacol. 2007 May;63(5):479-83. doi: 10.1007/s00228-007-0282-8. Epub 2007 Mar 8.

Abstract

Objective: To investigate the effect of efavirenz on the ketoconazole pharmacokinetics in HIV-infected patients.

Methods: Twelve HIV-infected patients were assigned into a one-sequence, two-period pharmacokinetic interaction study. In phase one, the patients received 400 mg of ketoconazole as a single oral dose on day 1; in phase two, they received 600 mg of efavirenz once daily in combination with 150 mg of lamivudine and 30 or 40 mg of stavudine twice daily on days 2 to 16. On day 16, 400 mg of ketoconazole was added to the regimen as a single oral dose. Ketoconazole pharmacokinetics were studied on days 1 and 16.

Results: Pretreatment with efavirenz significantly increased the clearance of ketoconazole by 201%. C(max) and AUC(0-24) were significantly decreased by 44 and 72%, respectively. The T ((1/2)) was significantly shorter by 58%.

Conclusion: Efavirenz has a strong inducing effect on the metabolism of ketoconazole.

Publication types

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

MeSH terms

  • AIDS-Related Opportunistic Infections / drug therapy
  • Adult
  • Alkynes
  • Anti-HIV Agents / pharmacology*
  • Antifungal Agents / pharmacokinetics*
  • Area Under Curve
  • Benzoxazines / pharmacology*
  • Candidiasis, Oral / complications
  • Candidiasis, Oral / drug therapy
  • Cyclopropanes
  • Drug Interactions
  • Female
  • HIV Infections / complications
  • HIV Infections / drug therapy
  • Half-Life
  • Humans
  • Ketoconazole / pharmacokinetics*
  • Lamivudine
  • Male
  • Middle Aged
  • Stavudine

Substances

  • Alkynes
  • Anti-HIV Agents
  • Antifungal Agents
  • Benzoxazines
  • Cyclopropanes
  • Lamivudine
  • Stavudine
  • efavirenz
  • Ketoconazole