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慢性腎障害患者での肝輸送体OATP機能低下の機序と血漿中薬物濃度変化の定量的予測
https://doi.org/10.24517/00051700
https://doi.org/10.24517/00051700b6266013-5054-4cba-8e46-f37e1619d126
名前 / ファイル | ライセンス | アクション |
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PH-PR-MASUO-Y-kaken 2016-6p.pdf (185.3 kB)
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Item type | 報告書 / Research Paper(1) | |||||
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公開日 | 2018-07-19 | |||||
タイトル | ||||||
タイトル | 慢性腎障害患者での肝輸送体OATP機能低下の機序と血漿中薬物濃度変化の定量的予測 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Inhibitory mechanisms of hepatic uptake transporters/OATP during renal failure | |||||
言語 | ||||||
言語 | jpn | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_18ws | |||||
資源タイプ | research report | |||||
ID登録 | ||||||
ID登録 | 10.24517/00051700 | |||||
ID登録タイプ | JaLC | |||||
著者 |
増尾, 友佑
× 増尾, 友佑 |
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著者別表示 |
Masuo, Yusuke
× Masuo, Yusuke |
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提供者所属 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 金沢大学医薬保健研究域薬学系 | |||||
書誌情報 |
平成27(2015)年度 科学研究費補助金 若手研究(B) 研究成果報告書 en : 2015 Fiscal Year Final Research Report 巻 2014-04-01 - 2016-03-31, p. 6p., 発行日 2016-05-24 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | 一部の肝消失型薬物は、血中消失が慢性腎障害患者で遅延し、この原因として患者血漿中で蓄積する一部の尿毒素による肝膜輸送体のdirect inhibitionが報告されているが、他の尿毒素による阻害やdirect inhibition以外の作用は未解明である。本研究では、p-cresyl sulfateによる肝膜輸送体OATP1B1のdirect inhibitionとindoxyl sulfateによるOATP1B1のlong-lasting inhibitionを明らかにした。本研究で明らかになった阻害作用は、慢性腎障害時におけるOATP1B1基質薬の血中消失の遅延を一部説明しうるものである。 | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Several uremic toxins have been proposed to inhibit hepatic uptake transporters. The purpose is to clarify possible long-lasting inhibition of OATP1B1 by uremic toxins. OATP1B1-mediated uptake of [3H]estrone sulfate (E3S) was examined after co-incubation or preincubation with uremic toxins in HEK293/OATP1B1 cells and primary cultured human hepatocytes. Among 21 uremic toxins, indoxyl sulfate (IS), CMPF and p-cresyl sulfate directly inhibited OATP1B1 mediated-uptake of E3S, but only IS exhibited inhibitory effect even after preincubation. Such inhibition of E3S uptake by preincubation with IS was more remarkable than that by its co-incubation, and observed in preincubation time- and concentration-dependent manners. Preincubation with IS also decreased uptake of E3S in human hepatocytes in primary culture. Overall, the long-lasting inhibition in the presence of IS could at least partially explain the delayed elimination of OATP1B1 substrate drugs during severe renal failure. | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 研究課題/領域番号:26860099, 研究期間(年度):2014-04-01 - 2016-03-31 | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 出典:研究課題「慢性腎障害患者での肝輸送体OATP機能低下の機序と血漿中薬物濃度変化の定量的予測」課題番号26860099 (KAKEN:科学研究費助成事業データベース(国立情報学研究所)) (https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-26860099/26860099seika/)を加工して作成 |
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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 | |||||
関連URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://kaken.nii.ac.jp/search/?qm=90708140 | |||||
関連名称 | https://kaken.nii.ac.jp/search/?qm=90708140 | |||||
関連URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-26860099/ | |||||
関連名称 | https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-26860099/ | |||||
関連URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-26860099/26860099seika/ | |||||
関連名称 | https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-26860099/26860099seika/ |