Culture Period-Dependent Changes in the Uptake of Transporter Substrates in Sandwich-Cultured Rat and Human Hepatocytes
文献类型：期刊论文
| 作者 | Kotani, Naoki; Maeda, Kazuya; Watanabe, Takao; Hiramatsu, Mariko; Gong, Li-kun2 ; Bi, Yi-an1; Takezawa, Toshiaki4; Kusuhara, Hiroyuki; Sugiyama, Yuichi3
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| 刊名 | DRUG METABOLISM AND DISPOSITION
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| 出版日期 | 2011-09 |
| 卷号 | 39期号:9页码:1503-1510 |
| ISSN号 | 0090-9556 |
| DOI | 10.1124/dmd.111.038968 |
| 文献子类 | Article |
| 英文摘要 | Sandwich-cultured hepatocytes (SCH) are a useful tool for evaluating hepatobiliary drug transport in vitro. Some studies have investigated the in vitro-in vivo correlations of the biliary clearance of drugs using SCH. In most cases, the biliary clearance observed in vivo correlated well with the predicted clearance, but the predicted absolute values were underestimated when based on in vitro experiments with SCH. We hypothesized that the down-regulated function of uptake transporters is one of the causes of this underestimation. Therefore, the uptake of taurocholate, digoxin, pravastatin, and rosuvastatin was investigated in sandwich-cultured rat hepatocytes (SCRH) cultured for 5, 24, 48, and 96 h, and the predicted hepatic clearance from in vitro uptake clearance (CLH, vitro) was calculated with a dispersion model. In SCRH cultured for 96 h, the saturable uptake of taurocholate, digoxin, pravastatin, and rosuvastatin decreased to 7.5, 3.3, 64, and 23%, respectively, of their uptake in hepatocytes cultured for 5 h, and a better prediction of in vivo hepatic clearance (CLH, vivo) was achieved when based on CLH, vitro of 5-h-cultured hepatocytes. These results suggest that the uptake activity is considerably reduced in cell culture, even in a sandwich-culture format. In a similar study, we also examined taurocholate and rosuvastatin in sandwich-cultured human hepatocytes (SCHH). Unlike in SCRH, the saturable uptake of these compounds did not differ markedly in SCHH cultured for 5 or 96 h. Thus, the uptake activity in SCHH was maintained relatively well compared with that in SCRH. |
| WOS关键词 | MICROSOMAL-ENZYME ACTIVITY ; COA REDUCTASE INHIBITOR ; IN-VIVO CORRELATION ; BILIARY-EXCRETION ; HEPATOBILIARY DISPOSITION ; HEPATIC ELIMINATION ; DRUG CLEARANCE ; BLOOD-FLOW ; LIVER ; EXPRESSION |
| 资助项目 | Ministry of Health, Labor and Welfare of Japan[00000000] ; Japan Society for the Promotion of Science[20249008] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000294050900005 |
| 出版者 | AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278425]  |
| 专题 | 药物安全性评价中心 |
| 通讯作者 | Sugiyama, Yuichi |
| 作者单位 | 1.Pfizer Global Res & Dev, Groton, CT USA; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Safety & Evaluat Res, State Key Lab New Drug Res, Shanghai 200031, Peoples R China; 3.Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Mol Pharmacokinet, Bunkyo Ku, Tokyo 1130033, Japan; 4.Natl Inst Agrobiol Sci, Lab Anim Cell Biol, Ibaraki, Japan |
| 推荐引用方式 GB/T 7714 | Kotani, Naoki,Maeda, Kazuya,Watanabe, Takao,et al. Culture Period-Dependent Changes in the Uptake of Transporter Substrates in Sandwich-Cultured Rat and Human Hepatocytes[J]. DRUG METABOLISM AND DISPOSITION,2011,39(9):1503-1510. |
| APA | Kotani, Naoki.,Maeda, Kazuya.,Watanabe, Takao.,Hiramatsu, Mariko.,Gong, Li-kun.,...&Sugiyama, Yuichi.(2011).Culture Period-Dependent Changes in the Uptake of Transporter Substrates in Sandwich-Cultured Rat and Human Hepatocytes.DRUG METABOLISM AND DISPOSITION,39(9),1503-1510. |
| MLA | Kotani, Naoki,et al."Culture Period-Dependent Changes in the Uptake of Transporter Substrates in Sandwich-Cultured Rat and Human Hepatocytes".DRUG METABOLISM AND DISPOSITION 39.9(2011):1503-1510. |
入库方式： OAI收割
来源：上海药物研究所
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