title: An update on metabolism studies using human hepatocytes in primary culture.
abstract: BACKGROUND
  Cultured human hepatocytes are the closest in vitro model to human liver and constitute a very predictive model for drug metabolism in vivo. The variability observed in human hepatocytes reflects the existing phenotypic heterogeneity of cytochrome P450 expression in human liver.
  
  
  OBJECTIVE
  As drug metabolism is the major source of pharmacokinetic variability in human beings, the main areas of current drug metabolism research in human hepatocytes are reviewed.
  
  
  METHODS
  To speed up the selection of drug candidates, the evaluation of metabolic stability, metabolite profiling and identification, and drug-drug interaction potential are key issues in drug development.
  
  
  CONCLUSIONS
  In vitro drug metabolism studies, which are inexpensive and readily carried out, serve as an adequate screening mechanism to characterize drug metabolites, elucidate their pathways, and make suggestions for further in vivo testing.
authors.affiliation: Unidad de Hepatología Experimental, Centro de Investigación, Hospital La Fe, Avda de Campanar 21, 46009-Valencia, Spain. gomez_mjo@gva.es
authors.forename: María José
authors.initials: MJ
authors.lastname: Gómez-Lechón
authors.forename: José V
authors.initials: JV
authors.lastname: Castell
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Donato
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D022781:Hepatocytes / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System