Stereospecific analysis of omeprazole supports artemisinin as a potent inducer of CYP2C19

Fundam Clin Pharmacol. 1999;13(6):671-5. doi: 10.1111/j.1472-8206.1999.tb00379.x.


The purpose of the study was to determine the enantiomer pharmacokinetics of omeprazole and 5-hydroxy-omeprazole before and after administration of the antimalarial artemisinin to confirm artemisinin's ability to induce CYP2C19. Nine healthy male Vietnamese subjects were given a single 20 mg dose of omeprazole orally 1 week before (day - 7) artemisinin administration. Artemisinin was then given orally (500 mg) for 7 days (days 1-7). On days 1 and 7, a single 20 mg dose of omeprazole was coadministered with artemisinin. After a washout period of 6 days, a single 20 mg dose of omeprazole was again administered together with a single 500 mg of artemisinin (day 14). Stereoselective pharmacokinetics of omeprazole and 5-hydroxyomeprazole was determined on days of omeprazole administration. Seven days of artemisinin administration significantly decreased the AUC of both omeprazole enantiomers (day 7), compared with day 1 (P < 0.001). All values were normalized after the washout period. Artemisinin increased the AUC ratio of R-5-hydroxyomeprazole/R-omeprazole significantly (P < 0.01) on day 7. The AUC ratio of omeprazole sulphone/S-omeprazole did not differ between study days. Artemisinin decreased the AUC of S-omeprazole to the same extent as that of R-omeprazole in extensive CYP2C19 metabolizers. suggesting that artemisinin induces a different enzyme in addition to CYP2C19. These results support and strengthen earlier findings that artemisinin induces CYP2C19 as well as at least one enzyme other than CYP3A4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Antimalarials / pharmacology*
  • Area Under Curve
  • Artemisinins*
  • Aryl Hydrocarbon Hydroxylases*
  • Chromatography, High Pressure Liquid
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 Enzyme Inhibitors*
  • Drug Interactions
  • Enzyme Inhibitors / blood
  • Enzyme Inhibitors / pharmacokinetics*
  • Humans
  • Male
  • Mixed Function Oxygenases / antagonists & inhibitors*
  • Omeprazole / analogs & derivatives*
  • Omeprazole / blood
  • Omeprazole / pharmacokinetics*
  • Sesquiterpenes / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship


  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Antimalarials
  • Artemisinins
  • Cytochrome P-450 Enzyme Inhibitors
  • Enzyme Inhibitors
  • Sesquiterpenes
  • 5-hydroxymethylomeprazole
  • artemisinine
  • Mixed Function Oxygenases
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Omeprazole