caa a22 4500 477128106 CHVBK 20180405111655.0 cr unu---uuuuu 170330e19970201xx s 000 0 eng 10.1023/A:1012036324237 doi (NATIONALLICENCE)springer-10.1023/A:1012036324237 The Use of Human Hepatocytes to Select Compounds Based on Their Expected Hepatic Extraction Ratios in Humans [Elektronische Daten] [Th. Lavé, S. Dupin, C. Schmitt, B. Valles, G. Ubeaud, R. Chou, D. Jaeck, Ph. Coassolo] Purpose. The present investigation retrospectively evaluates the use of human hepatocytes to classify compounds into low, intermediate or high hepatic extraction ratio in man. Methods. A simple approach was used to correlate the in vivo hepatic extraction ratio of a number of compounds in man (literature and in-house data) with the corresponding in vitro clearance which was determined in human hepatocytes. The present approach assumes that, for compounds eliminated mainly through liver metabolism, intrinsic clearance is the major determinant for their in vivo hepatic extraction ratio and subsequently their bioavailability in man. The test compounds were selected to represent a broad range of extraction ratios and a variety of metabolic pathways. Results. The present data show that in vitro clearances in human hepatocytes are predictive for the hepatic extraction ratios in vivo in man. Most of the test compounds (n = 19) were successfully classified based upon human hepatocyte data into low, intermediate or high hepatic extraction compounds, i.e. compounds with potential for high, intermediate or low bioavailabilities in humans. Conclusions. The present approach, validated so far with 19 test compounds, appears to be a valuable tool to screen for compounds with respect to liver first-pass metabolism at an early phase of drug discovery. Plenum Publishing Corporation, 1997 human hepatocytes nationallicence extraction ratio nationallicence pharmacokinetics nationallicence clearance nationallicence in vitro models nationallicence Lavé Th aut Dupin S. aut Schmitt C. aut Valles B. aut Ubeaud G. aut Chou R. aut Jaeck D. aut Coassolo Ph aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/2(1997-02-01), 152-155 0724-8741 14:2<152 1997 14 11095 https://doi.org/10.1023/A:1012036324237 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012036324237 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Lavé Th aut NATIONALLICENCE 700 1- Dupin S. aut NATIONALLICENCE 700 1- Schmitt C. aut NATIONALLICENCE 700 1- Valles B. aut NATIONALLICENCE 700 1- Ubeaud G. aut NATIONALLICENCE 700 1- Chou R. aut NATIONALLICENCE 700 1- Jaeck D. aut NATIONALLICENCE 700 1- Coassolo Ph aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/2(1997-02-01), 152-155 0724-8741 14:2<152 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer