TY - JOUR T1 - In Vitro–In Vivo Correlation for Low-Clearance Compounds Using Hepatocyte Relay Method JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 2018 LP - 2023 DO - 10.1124/dmd.113.053322 VL - 41 IS - 12 AU - Li Di AU - Karen Atkinson AU - Christine C. Orozco AU - Carrie Funk AU - Hui Zhang AU - Thomas S. McDonald AU - Beijing Tan AU - Jian Lin AU - Cheng Chang AU - R. Scott Obach Y1 - 2013/12/01 UR - http://dmd.aspetjournals.org/content/41/12/2018.abstract N2 - In vitro–in vivo correlation (IVIVC) of intrinsic clearance in preclinical species of rat and dog was established using the hepatocyte relay method to support high-confidence prediction of human pharmacokinetics for low-clearance compounds. Good IVIVC of intrinsic clearance was observed for most of the compounds, with predicted values within 2-fold of the observed values. The exceptions involved transporter-mediated uptake clearance or metabolizing enzymes with extensive extrahepatic contribution. This is the first assay available to address low clearance challenges in preclinical species for IVIVC in drug discovery. It extends the utility of the hepatocyte relay method in addressing low clearance issues. ER -