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

The purpose of the study was to determine the enantiomer pharmacokinetics o f omeprazole and 5-hydroxy-omeprazole before and after administration of th e antimalarial artemisinin to confirm artemisinin's ability to induce CYP2C 19. Nine healthy male Vietnamese subjects were given a single 20 mg dose of omeprazole orally 1 week before (day -7) artemisinin administration. Artem isinin 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. A fter a washout period of 6 days, a single 20 mg dose of omeprazole was agai n administered together with a single 500 mg of artemisinin (day 14). Stere oselective pharmacokinetics of omeprazole and 5-hydroxyomeprazole was deter mined on days of omeprazole administration. Seven days of artemisinin admin istration significantly decreased the AUC of both omeprazole enantiomers (d ay 7), compared with day 1 (P < 0.001). All values were normalized after th e washout period. Artemisinin increased the AUC ratio of R-5-hydroxyomepraz ole/R-omeprazole significantly (P < 0.01) on day 7. The AUC ratio of omepra zole sulphone/S-omeprazole did not differ between study days. Artemisinin d ecreased the AUC of S-omeprazole to the same extent as that of R-omeprazole in extensive CYP2C19 metabolizers, suggesting that artemisinin induces a d ifferent enzyme in addition to CYP2C19. These results support and strengthe n earlier findings that artemisinin induces CYP2C19 as well as at least one enzyme other than CYP3A4. (C) 1999 Editions scientifiques et medicales Els evier SAS.