An update on metabolism studies using human hepatocytes in primary culture.
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.
Gómez-Lechón
María José
MJ
Unidad de Hepatología Experimental, Centro de Investigación, Hospital La Fe, Avda de Campanar 21, 46009-Valencia, Spain. gomez_mjo@gva.es
Castell
José V
JV
Donato
María Teresa
MT
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
D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System