Stereospecific analysis of omeprazole supports artemisinin as a potent inducer of CYP2C19
| Autor: | Michael Ashton, Ulrika S H Svensson, Leif Bertilsson, Kazuo Mihara, Trinh Ngoc Hai, Gunnel Tybring |
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| Rok vydání: | 2000 |
| Předmět: |
Male
medicine.drug_class Proton-pump inhibitor CYP2C19 Pharmacology 2-Pyridinylmethylsulfinylbenzimidazoles Mixed Function Oxygenases Antimalarials Structure-Activity Relationship Pharmacokinetics Oral administration parasitic diseases medicine Cytochrome P-450 Enzyme Inhibitors Humans Pharmacology (medical) Drug Interactions Artemisinin Enzyme Inhibitors Omeprazole Chromatography High Pressure Liquid CYP3A4 Chemistry Stereoisomerism Drug interaction Artemisinins Cytochrome P-450 CYP2C19 Area Under Curve Aryl Hydrocarbon Hydroxylases Sesquiterpenes medicine.drug |
| Zdroj: | Fundamentalclinical pharmacology. 13(6) |
| ISSN: | 0767-3981 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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