Stereospecific analysis of omeprazole supports artemisinin as a potent inducer of CYP2C19
Stereospecific analysis of omeprazole supports artemisinin as a potent inducer of CYP2C19
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DOI：
10.1111/j.1472-8206.1999.tb00379.x
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发表时间：
1999-01-01
影响因子：
2.9
通讯作者：
Ashton, M
中科院分区：
文献类型：
--
作者：
Mihara, K;Svensson, USH;Ashton, M
本研究的目的是确定奥美拉唑和5-羟基-奥美拉唑在抗疟药青蒿素给药前后的对映体药代动力学，以证实青蒿素诱导CYP 2C 19的能力。9名健康越南男性受试者在青蒿素给药前1周（第-7天）单次口服20 mg奥美拉唑。然后口服青蒿素（500 mg）7天（第1-7天）。在第1天和第7天，单次给予20 mg奥美拉唑与青蒿素。6天洗脱期后，再次给予单次20 mg奥美拉唑和单次500 mg青蒿素（第14天）。在奥美拉唑给药日测定奥美拉唑和5-羟基奥美拉唑的立体选择性药代动力学。青蒿素给药7天后，两种奥美拉唑对映体的AUC（第7天）与第1天相比均显著降低（P < 0.001）。洗脱期后，所有数值均正常化。青蒿素组第7天R-5-羟基奥美拉唑/R-奥美拉唑的AUC比值显著增加（P < 0.01）。奥美拉唑砜/S-奥美拉唑的AUC比值在研究日之间无差异。青蒿素降低S-奥美拉唑AUC的程度与CYP 2C 19强代谢者中R-奥美拉唑相同，表明青蒿素诱导CYP 2C 19以外的不同酶。这些结果支持并加强了早期的发现，即青蒿素诱导CYP 2C 19以及至少一种CYP 3A 4以外的酶。(C)1999年科学与医学版Elsevier SAS。
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. (C) 1999 Editions scientifiques et medicales Elsevier SAS.