More Relevant Prediction for In Vivo Drug Interaction of Candesartan Cilexetil on Hepatic Bile Acid Transporter BSEP Using Sandwich-cultured Hepatocytes
-
- FUKUDA Hajime
- Department of Membrane Transport and Biopharmaceutics, Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University
-
- NAKANISHI Takeo
- Department of Membrane Transport and Biopharmaceutics, Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University
-
- TAMAI Ikumi
- Department of Membrane Transport and Biopharmaceutics, Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University
書誌事項
- タイトル別名
-
- More Relevant Prediction for <i>In Vivo</i> Drug Interaction of Candesartan Cilexetil on Hepatic Bile Acid Transporter BSEP Using Sandwich-cultured Hepatocytes
この論文をさがす
抄録
Bile salt export pump (BSEP) plays a major role in biliary secretion of bile salts; therefore, drug-induced cholestasis could occur because of BSEP inhibition by drugs. Drug interaction on hepatic bile canalicular transporters such as BSEP with prodrugs that are rapidly metabolized has not been evaluated well. In the present study, candesartan cilexetil (CIL) was used as a model compound and its inhibitory potential against BSEP was determined in sandwich-cultured human hepatocytes (hSCH) as well as in BSEP-expressing membrane vesicles. CIL exhibited potent BSEP inhibition with an IC50 value of 6.2 µM in the transport assay using membrane vesicles. In contrast, BSEP inhibition by CIL was not observed in hSCH after 120 min exposure. This discordance is possibly explained by metabolic elimination of CIL in hSCH because BSEP inhibition became reversely pronounced under the conditions where CIL metabolism was suppressed by diisopropyl fluorophosphates. The results observed in hSCH are consistent with the fact that liver dysfunction or jaundice occurs with low frequency in clinical use of CIL, which may not be obtained by membrane vesicle study on the effect of CIL on BSEP.<br>
収録刊行物
-
- Ｄｒｕｇ Ｍｅｔａｂｏｌｉｓｍ ａｎｄ Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ
-
Ｄｒｕｇ Ｍｅｔａｂｏｌｉｓｍ ａｎｄ Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ 29 (1), 94-96, 2014
日本薬物動態学会