Primary hepatocytes: current understanding of the regulation of metabolic enzymes and transporter proteins, and pharmaceutical practice for the use of hepatocytes in metabolism, enzyme induction, transporter, clearance, and hepatotoxicity studies

Drug Metab Rev. 2007;39(1):159-234. doi: 10.1080/03602530601093489.


This review brings you up-to-date with the hepatocyte research on: 1) in vitro-in vivo correlations of metabolism and clearance; 2) CYP enzyme induction, regulation, and cross-talk using human hepatocytes and hepatocyte-like cell lines; 3) the function and regulation of hepatic transporters and models used to elucidate their role in drug clearance; 4) mechanisms and examples of idiosyncratic and intrinsic hepatotoxicity; and 5) alternative cell systems to primary human hepatocytes. We also report pharmaceutical perspectives of these topics and compare methods and interpretations for the drug development process.

Publication types

  • Review

MeSH terms

  • Animals
  • Carrier Proteins / metabolism*
  • Chemical and Drug Induced Liver Injury
  • Cytochrome P-450 Enzyme System / metabolism*
  • Drug-Related Side Effects and Adverse Reactions
  • Hepatocytes / cytology
  • Hepatocytes / enzymology*
  • Hepatocytes / metabolism*
  • Humans
  • Liver Diseases / metabolism
  • Metabolic Clearance Rate
  • Models, Biological
  • Pharmaceutical Preparations / administration & dosage
  • Pharmaceutical Preparations / metabolism
  • Xenobiotics / adverse effects
  • Xenobiotics / metabolism
  • Xenobiotics / pharmacokinetics


  • Carrier Proteins
  • Pharmaceutical Preparations
  • Xenobiotics
  • Cytochrome P-450 Enzyme System