Journal
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
Volume 4, Issue 7, Pages 837-854Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1517/17425255.4.7.837
Keywords
cytochrome P450; drug metabolism; human hepatocytes; P450 induction; P450 inhibition
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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. Objectives: 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. Results/conclusion: 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.
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