| アブストラクト | Omeprazole, a gastric acid pump inhibitor, is repeatedly administered and is oxidatively metabolized mainly by polymorphic cytochrome P450 2C19. The prescribed dosage of omeprazole was discontinued or reduced in 47 of the 135 patients who received omeprazole alone in this survey, as recorded in the Japanese Adverse Drug Event Report database. The days to onset of omeprazole-related disorders were 3-4 d (median) and 16 d for intravenous 20-40 mg and oral 20 mg daily doses, respectively, in 34 patients for whom relevant data were available. The maximum plasma concentration of omeprazole was pharmacokinetically modeled after a single oral 40-mg dose in P450 2C19-defective poor metabolizers and was 2.4-fold higher than that in extensive metabolizers. The modeled area under the hepatic concentration curves of omeprazole in P450 2C19 poor metabolizers after virtual daily 40-mg doses for 7 d was 5.2-fold higher than that in the extensive metabolizers. Omeprazole-induced P450 2C19 (approx. 2-fold), resulting in increased hepatic intrinsic clearance in repeated doses, was considered after the second day. Virtual plasma/hepatic exposure estimated using pharmacokinetic modeling in subjects with P450 2C19 poor metabolizers indicated that these exposure levels virtually estimated could be one of causal factors for unexpected hepatic disorders induced by prescribed omeprazole, such as those resulting from drug interactions with repeatedly co-administered medicines. |
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| ジャーナル名 | Biological & pharmaceutical bulletin |
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| Pubmed追加日 | 2024/5/27 |
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| 投稿者 | Adachi, Koichiro; Ohyama, Katsuhiro; Tanaka, Yoichi; Murayama, Norie; Shimizu, Makiko; Saito, Yoshiro; Yamazaki, Hiroshi |
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| 組織名 | Showa Pharmaceutical University.;School of Pharmacy, Tokyo University of Pharmacy and Life Sciences.;National Institute of Health Sciences. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/38797695/ |
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