Department of Pharmaceutics, University of Washington, Seattle, Washington (K.I., J.D.U.); Cellular Transport Group, Pharmaceutical Sciences, Roche Innovation Centre Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland (M.U.); and SOLVO Biotechnology, Budaörs, Hungary (B.T., V.J.).
Department of Pharmaceutics, University of Washington, Seattle, Washington (K.I., J.D.U.); Cellular Transport Group, Pharmaceutical Sciences, Roche Innovation Centre Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland (M.U.); and SOLVO Biotechnology, Budaörs, Hungary (B.T., V.J.)
Drug Metab Dispos. 2018 Jan;46(1):66-74. doi: 10.1124/dmd.117.076539. Epub 2017 Oct 30.
We determined whether in vivo transporter-mediated hepatobiliary clearance (CL) and hepatic concentrations of rosuvastatin (RSV) in the rat could be predicted by transport activity in sandwich-cultured rat hepatocytes (SCRHs) and/or transporter-expressing cell lines scaled by differences in transporter protein expression between SCRHs, cell lines, and rat liver. The predicted hepatobiliary CLs and hepatic concentrations of RSV were compared with our previously published positron emission tomography imaging data. Sinusoidal uptake CL ([Formula: see text] [Formula: see text] [Formula: see text] [Formula: see text] [Formula: see text] [Formula: see text] for Oatp protein expression. This is the first demonstration of the successful prediction of in vivo hepatobiliary CLs and hepatic concentrations of RSV using transporter-expressing cells and SCRHs.
我们研究了能否通过三明治培养的大鼠肝细胞（SCRHs）中的转运活性和/或根据SCRHs、细胞系与大鼠肝脏之间转运蛋白表达差异进行缩放的转运蛋白表达细胞系，来预测大鼠体内转运体介导的罗苏伐他汀（RSV）肝胆清除率（CL）和肝脏浓度。将预测的RSV肝胆CL值和肝脏浓度与我们之前发表的正电子发射断层扫描成像数据进行比较。窦状隙摄取CL（[公式：见正文] [公式：见正文] [公式：见正文] [公式：见正文] [公式：见正文] [公式：见正文] 用于Oatp蛋白表达。这是首次证明使用转运蛋白表达细胞和SCRHs成功预测了RSV的体内肝胆CL值和肝脏浓度。
