Impact of efavirenz on intestinal metabolism and transport: Insights from an interaction study with ezetimibe in healthy volunteers

S. Oswald, H. E. Meyer Zu Schwabedissen, A. Nassif, C. Modess, Z. Desta, E. T. Ogburn, J. Mostertz, M. Keiser, J. Jia, A. Hubeny, A. Ulrich, D. Runge, M. Marinova, D. Lütjohann, H. K. Kroemer, W. Siegmund

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Hypercholesterolemia frequently occurs in patients treated with efavirenz who cannot be treated adequately with statins because of drug interactions. These patients may benefit from cholesterol-lowering therapy with ezetimibe. This study determined the influence of single-dose and multiple-dose efavirenz (400 mg/day for 9 days) on the pharmacokinetics and sterol-lowering of ezetimibe (10 mg) in 12 healthy subjects. In addition, the influence of efavirenz on genome-wide intestinal expression and in vitro function of ABCB1, ABCC2, UGT1A1, and OATP1B1 was studied. Efavirenz (multiple dose) had no influence on the pharmacokinetics and lipid-lowering functions of ezetimibe. Intestinal expression of enzymes and transporters (e.g., ABCB1, ABCC2, and UGT1A1) was not affected by chronic efavirenz. Efavirenz (single dose) slightly increased ezetimibe absorption and markedly decreased exposure to ezetimibe-glucuronide (single dose and multiple dose), which may be explained by inhibition of UGT1A1 and ABCB1 (in vitro data). Ezetimibe had no effect on the disposition of efavirenz. Consequently, ezetimibe may be a safe and efficient therapeutic option in patients with HIV infection.

Original languageEnglish (US)
Pages (from-to)506-513
Number of pages8
JournalClinical Pharmacology and Therapeutics
Volume91
Issue number3
DOIs
StatePublished - Mar 1 2012

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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    Oswald, S., Meyer Zu Schwabedissen, H. E., Nassif, A., Modess, C., Desta, Z., Ogburn, E. T., Mostertz, J., Keiser, M., Jia, J., Hubeny, A., Ulrich, A., Runge, D., Marinova, M., Lütjohann, D., Kroemer, H. K., & Siegmund, W. (2012). Impact of efavirenz on intestinal metabolism and transport: Insights from an interaction study with ezetimibe in healthy volunteers. Clinical Pharmacology and Therapeutics, 91(3), 506-513. https://doi.org/10.1038/clpt.2011.255