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Involvement of the drug transporters P glycoprotein and multidrug resistance-associated protein Mrp2 in Telithromycin transport
http://hdl.handle.net/2237/10683
http://hdl.handle.net/2237/106835fcfa354-0d37-4860-a97b-4ae8d274ccaa
名前 / ファイル | ライセンス | アクション |
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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公開日 | 2008-12-01 | |||||
タイトル | ||||||
タイトル | Involvement of the drug transporters P glycoprotein and multidrug resistance-associated protein Mrp2 in Telithromycin transport | |||||
言語 | en | |||||
その他のタイトル | ||||||
その他のタイトル | テリスロマイシンの生体膜輸送機構における薬物トランスポーター糖蛋白質および多剤耐性関連蛋白(Mrp2)への関与 | |||||
言語 | ja | |||||
著者 |
山口, 昌之
× 山口, 昌之× Yamaguchi, Shoji |
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アクセス権 | ||||||
アクセス権 | open access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
抄録 | ||||||
内容記述 | The preset study aims to investigate the role of P glycoprotein and multidrug resistance-associated protein (Mrp2) in the transport of telithromycin, a newly developed ketolide antibiotic, in vitro and in vivo. The in vitro experiments revealed that the intracellular accumulation of telithromycin in adriamycin-resistant human chronic myelogenous leukemia cells (K562/ADR) overexpressing P glycoprotein was significantly lower than that in human chronic myelogenous leukemia cells (K562/S) not expressing P glycoprotein. Cyclosporine significantly increased the intracellular accumulation of telithromycin in K562/ADR cells. When telithromycin was coadministered intravenously with cyclosporine in Sprague-Dawley (SD) rats, cyclosporine significantly delayed the disappearance of telithromycin from plasma and decreased its systemic clearance to 60% of the corresponding control values. Hepatobiliary excretion experiments revealed that cyclosporine almost completely inhibited the biliary clearance of telithromycin, suggesting that telithromycin is a substrate of P glycoprotein and a potential substrate of Mrp2. Moreover, the biliary clearance of telithromycin was significantly decreased by 80% in Eisai hyperbilirubinemic mutant rats with a hereditary deficiency in Mrp2, indicating that Mrp2, as well as P glycoprotein, plays an important role in the biliary excretion of telithromycin. When the effect of telithromycin on the biliary excretion of doxorubicin, a substrate of P glycoprotein and Mrp2, was examined in SD rats, telithromycin significantly decreased the biliary clearance of doxorubicin by 80%. Results obtained from this study indicate that telithromycin is a substrate of both P glycoprotein and Mrp2, and these transporters are involved in the hepatobiliary transport of telithromycin. | |||||
言語 | en | |||||
内容記述タイプ | Abstract | |||||
内容記述 | ||||||
内容記述 | 名古屋大学博士学位論文 学位の種類:博士(医療技術学) (課程) 学位授与年月日:平成19年3月23日 | |||||
言語 | ja | |||||
内容記述タイプ | Other | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源 | http://purl.org/coar/resource_type/c_db06 | |||||
タイプ | doctoral thesis | |||||
書誌情報 |
発行日 2007-03-23 |
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学位名 | ||||||
言語 | ja | |||||
学位名 | 博士(医療技術学) | |||||
学位授与機関 | ||||||
学位授与機関識別子Scheme | kakenhi | |||||
学位授与機関識別子 | 13901 | |||||
言語 | ja | |||||
学位授与機関名 | 名古屋大学 | |||||
言語 | en | |||||
学位授与機関名 | NAGOYA University | |||||
学位授与年度 | ||||||
学位授与年度 | 2006 | |||||
学位授与年月日 | ||||||
学位授与年月日 | 2007-03-23 | |||||
学位授与番号 | ||||||
学位授与番号 | 甲第7282号 | |||||
フォーマット | ||||||
application/pdf | ||||||
著者版フラグ | ||||||
値 | publisher | |||||
URI | ||||||
識別子 | http://hdl.handle.net/2237/10683 | |||||
識別子タイプ | HDL |