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Utilization of Liver Microsomes to Estimate Hepatic Intrinsic Clearance of Monoamine Oxidase Substrate Drugs in Humans
http://hdl.handle.net/2297/47882
http://hdl.handle.net/2297/4788257f23762-8f3f-46c2-9fea-963fb2298968
名前 / ファイル | ライセンス | アクション |
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PH-PR-KATO-Y-1233.pdf (259.1 kB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2017-12-05 | |||||
タイトル | ||||||
タイトル | Utilization of Liver Microsomes to Estimate Hepatic Intrinsic Clearance of Monoamine Oxidase Substrate Drugs in Humans | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Masuo, Yusuke
× Masuo, Yusuke× Nagamori, Shushi× Hasegawa, Aoi× Hayashi, Kazuki× Isozumi, Noriyoshi× Nakamichi, Noritaka× Kanai, Yoshikatsu× Kato, Yukio |
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書誌情報 |
Pharmaceutical Research 巻 34, 号 6, p. 1233-1243, 発行日 2017-06-01 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0724-8741 | |||||
NCID | ||||||
収録物識別子タイプ | NCID | |||||
収録物識別子 | AA10632083 | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1007/s11095-017-2140-4 | |||||
出版者 | ||||||
出版者 | Springer | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Purpose: Monoamine oxidases (MAOs) are non-CYP enzymes that contribute to systemic elimination of therapeutic agents, and localized on mitochondrial membranes. The aim of the present study was to validate quantitative estimation of metabolic clearance of MAO substrate drugs using human liver microsomes (HLMs). Methods: Three MAO substrate drugs, sumatriptan, rizatriptan and phenylephrine, as well as four CYP substrates were selected, and their disappearance during incubation with HLMs or mitochondria (HLMt) was measured. Metabolic clearance (CL) was then calculated from the disappearance curve. Results: CL obtained in HLMs for sumatriptan and a typical MAO substrate serotonin was correlated with that obtained in HLMt among ten human individual livers. Hepatic intrinsic clearance (CLint,vitro) estimated from CL in HLMs was 14–20 and 2–5 times lower than in vivo hepatic intrinsic clearance (CLint,vivo) obtained from literature for MAO and CYP substrates, respectively. Utilization of HLMs for quantitatively assessing metabolic clearance of MAO substrates was further validated by proteomics approach which has revealed that numerous proteins localized on inner and outer membranes of mitochondria were detected in both HLMs and HLMt. Conclusion: CLint,vitro values of MAO substrate drugs can be quantitatively estimated with HLMs and could be used for semi-quantitative prediction of CLint,vivo values. © 2017 Springer Science+Business Media New York | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Embargo Period 12 months | |||||
権利 | ||||||
権利情報 | © 2017 Springer Science+Business Media New York | The final publication is available at www.springerlink.com/article/10.1007/s11095-017-2140-4 | |||||
著者版フラグ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa |