Inhibitory Effect of Antituberculosis Drugs on Human Cytochrome P450-Mediated Activities
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概要
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The potential for drug-drug interactions mediated by the inhibition of cytochrome P-450 (CYP) were concerned during antituberculosis therapy. However, the information regarding human CYP inhibition by antituberculosis drugs is limited to isoniazid. In the current study, we examined the inhibitory effects of pyrazinamide and ethionamide, both of which are chemically related to isoniazid, on the CYP-mediated activities in human liver microsomes (HLM) and compared them to that of isoniazid. No remarkable effects on any CYP activities were observed by pyrazinamide and ethionamide. In contrast, in addition to the reported inhibitory effect of isoniazid on CYP1A2, CYP2A6, CYP2C19, and CYP3A activities, our results newly showed its effect on CYP2C9 and CYP2E1 activities. Isoniazid showed potent direct inhibitory effect on S-warfarin 7-hydroxylation while a preincubation step in the presence of NADPH was needed to inhibit chlorzoxazone 6-hydroxylation. Furthermore, irreversible inhibition of CYP2C19 activity by isoniazid was also observed in the dilution study. These results suggested that pyrazinamide and ethionamide did not seem to cause drug interactions mediated by the inhibition of CYP. In contrast, isoniazid might contribute to the severe drug interactions by a different inhibitory mechanism depending on each of the CYP isozymes, in addition to the reported observations.
- 社団法人 日本薬理学会の論文
- 2004-11-20
著者
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YASUHARA Hajime
Department of Pharmacology, School of Medicine, Showa University
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Yasuhara Hajime
昭和大学 医学部第二薬理学教室
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Yasuhara H
Department Of Pharmacology School Of Medicine Showa University
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Yasuhara Hajime
Dep. Of Pharmacology School Of Medicine Showa Univ. Jpn
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Yasuhara Hajime
Department Of Pharmacology School Of Medicine Showa University:shionogi Research Laboratories Shiono
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Yasuhara Hajime
Department Of Second Pharmacology Showa University School Of Medicine
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Nishimura Yuki
Department of Cardiovascular and Renal Medicine, Saga University Faculty of Medicine
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KURATA NORIMITSU
Department of Biochemical Toxicology, School of Pharmaceutical Science Showa University
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Nishimura Yuki
Department Of Cardiovascular And Renal Medicine Saga University Faculty Of Medicine
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Nishimura Y
Department Of Pharmacology School Of Medicine Showa University
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SAKURAI Eriko
Department of Pharmacology, School of Medicine, Showa University
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Sakurai Eriko
Department Of Pharmacology School Of Medicine Showa University
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Kurata Norimitsu
Department Of Pharmacology School Of Medicine Showa University
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Kurata Norimitsu
Department Of Biochemical Toxicology School Of Pharmaceutical Science Showa University
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Yasuhara Hajime
Department Of Pharmacology School Of Medicine
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Yasuhara Hajime
Department Of Pediatrics Yao Municipal Hospital
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Yasuhara Hajime
Department Of Neonatal Intensive Care Unit Nara Prefectural Hospital
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