Induction of CYP2C19 and CYP3A activity following repeated administration of efavirenz in healthy volunteers

Clin Pharmacol Ther. 2012 Mar;91(3):475-82. doi: 10.1038/clpt.2011.249. Epub 2012 Feb 8.


Drug-drug interactions involving efavirenz are of major concern in clinical practice. We evaluated the effects of multiple doses of efavirenz on omeprazole 5-hydroxylation (CYP2C19) and sulfoxidation (CYP3A). Healthy volunteers (n = 57) were administered a single 20 mg oral dose of racemic omeprazole either with a single 600 mg oral dose of efavirenz or after 17 days of administration of 600 mg/day of efavirenz. The concentrations of racemic omeprazole, 5-hydroxyomeoprazole (and their enantiomers), and omeprazole sulfone in plasma were measured using a chiral liquid chromatography-tandem mass spectrometry method. Relative to single-dose treatment, multiple doses of efavirenz significantly decreased (P < 0.0001) the area under the plasma concentration-time curve from 0 to infinity (AUC(0-∞)) of racemic-, R- and S-omeprazole (2.01- to 2.15-fold) and the corresponding AUC(0-∞) metabolic ratio (MR) for 5-hydroxyomeprazole (1.36- to 1.44-fold) as well as the MR for omeprazole sulfone (∼2.0) (P < 0.0001). The significant reduction in the AUC of 5-hydroxyomeprazole after repeated efavirenz dosing suggests induction of sequential metabolism and mixed inductive/inhibitory effects of efavirenz on CYP2C19. In conclusion, efavirenz enhances omeprazole metabolism in a nonstereoselective manner through induction of CYP3A and CYP2C19 activity.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alkynes
  • Area Under Curve
  • Aryl Hydrocarbon Hydroxylases / biosynthesis*
  • Benzoxazines / administration & dosage*
  • Cyclopropanes
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP3A / biosynthesis*
  • Drug Interactions
  • Enzyme Induction / drug effects
  • Enzyme Inhibitors / blood
  • Enzyme Inhibitors / pharmacokinetics
  • Female
  • Humans
  • Hydroxylation
  • Male
  • Omeprazole / analogs & derivatives
  • Omeprazole / blood
  • Omeprazole / pharmacokinetics*
  • Reverse Transcriptase Inhibitors / pharmacology


  • Alkynes
  • Benzoxazines
  • Cyclopropanes
  • Enzyme Inhibitors
  • Reverse Transcriptase Inhibitors
  • omeprazole sulfone
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • CYP3A protein, human
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP3A
  • efavirenz
  • Omeprazole