Involvement of the drug transporters P glycoprotein and multidrug resistance-associated protein Mrp2 in Telithromycin transport

機関リポジトリ 機関リポジトリ (HANDLE) Web Site

書誌事項

タイトル
Involvement of the drug transporters P glycoprotein and multidrug resistance-associated protein Mrp2 in Telithromycin transport
タイトル別名
  • 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
著者
山口, 昌之
著者
Yamaguchi, Shoji
学位授与大学
名古屋大学
取得学位
博士(医療技術学)
学位授与番号
甲第7282号
学位授与年月日
2007-03-23

この論文をさがす

説明

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.

詳細情報 詳細情報について

問題の指摘

ページトップへ