caa a22 4500 465812570 CHVBK 20180323112120.0 cr unu---uuuuu 170327e19900401xx s 000 0 eng 10.1007/BF03190200 doi (NATIONALLICENCE)springer-10.1007/BF03190200 Human hepatocytes as a key in vitro model to improve preclinical drug development [Elektronische Daten] [Gerard Fabre, Jean Combalbert, Yves Berger, Jean Cano] Summary: Over past decades, numerous in vitro and/or ex vivo models have been developped to investigate drug metabolism. In the order of complexity we found the isolated perfused liver, hepatocytes in co-culture with epithelial cells, hepatocytes in suspension and in primary culture and subcellular hepatic microsomal fractions. Because they can be easily prepared from both animals (pharmacological and toxicological species) and humans (whole livers as well as biopsies obtained during surgery) hepatocytes in primary culture provide the most powerfull model to better elucidate drug behavior at an early stage of preclinical develompent such as: the characterization of main biotransformation reactions, the identification of phase I and phase II isozymes involved in such reactions, the evaluation of inter-species differences allowing the selection of a second toxicological animal species more closely related to man on the basis of metabolic profiles, the detection of the inducing and/or inhibitory effects of a drug on metabolic enzymes, the prediction of drug interactions, the estimation of inter-individual variability in biotransformation reactions. The use of hepatocytes, and in particular those obtained from humans, at an early stage of drug development allows the obtention of more predictive preclinical data and a better knowledge of drug behavior in humans before the first administration of the drug in healthy volunteers. Springer-Verlag, 1990 Human hepatocytes nationallicence in vitro investigation nationallicence preclinical drug development nationallicence Fabre Gerard SANOFI RECHERCHE Service de Métabolisme et de Pharmacocinétique, rue du Professeur Blayac, 34184, Montpellier,Cédex04, France aut Combalbert Jean SANOFI RECHERCHE Service de Métabolisme et de Pharmacocinétique, rue du Professeur Blayac, 34184, Montpellier,Cédex04, France aut Berger Yves SANOFI RECHERCHE Service de Métabolisme et de Pharmacocinétique, rue du Professeur Blayac, 34184, Montpellier,Cédex04, France aut Cano Jean SANOFI RECHERCHE Service de Métabolisme et de Pharmacocinétique, rue du Professeur Blayac, 34184, Montpellier,Cédex04, France aut European Journal of Drug Metabolism and Pharmacokinetics Springer-Verlag 15/2(1990-04-01), 165-171 0378-7966 15:2<165 1990 15 13318 https://doi.org/10.1007/BF03190200 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF03190200 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Fabre Gerard SANOFI RECHERCHE Service de Métabolisme et de Pharmacocinétique, rue du Professeur Blayac, 34184, Montpellier,Cédex04, France aut NATIONALLICENCE 700 1- Combalbert Jean SANOFI RECHERCHE Service de Métabolisme et de Pharmacocinétique, rue du Professeur Blayac, 34184, Montpellier,Cédex04, France aut NATIONALLICENCE 700 1- Berger Yves SANOFI RECHERCHE Service de Métabolisme et de Pharmacocinétique, rue du Professeur Blayac, 34184, Montpellier,Cédex04, France aut NATIONALLICENCE 700 1- Cano Jean SANOFI RECHERCHE Service de Métabolisme et de Pharmacocinétique, rue du Professeur Blayac, 34184, Montpellier,Cédex04, France aut NATIONALLICENCE 773 0- European Journal of Drug Metabolism and Pharmacokinetics Springer-Verlag 15/2(1990-04-01), 165-171 0378-7966 15:2<165 1990 15 13318 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer