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Stereospecific anal...
Stereospecific analysis of omeprazole supports artemisinin as a potent inducer of CYP2C19
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Mihara, K (author)
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- Svensson, Ulrika S H (author)
- Uppsala universitet,Institutionen för farmaci
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Tybring, G (author)
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Hai, T N (author)
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Bertilsson, L (author)
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Ashton, M (author)
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(creator_code:org_t)
- 1999
- 1999
- English.
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In: Fundamental & Clinical Pharmacology. - 0767-3981 .- 1472-8206. ; 13:6, s. 671-675
- Related links:
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https://urn.kb.se/re...
Abstract
Subject headings
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- 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.
Keyword
- artemisinin
- CYP2C19
- metabolism
- induction
- omeprazole
- enantiomers
Publication and Content Type
- ref (subject category)
- art (subject category)
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