Species comparison in P450 induction: effects of dexamethasone, omeprazole, and rifampin on P450 isoforms 1A and 3A in primary cultured hepatocytes from man, Sprague-Dawley rat, minipig, and beagle dog

Chem Biol Interact. 2001 May 16;134(3):271-81. doi: 10.1016/s0009-2797(01)00162-4.


Induction of P450 isoforms 1A (CYP1A) and 3A (CYP3A) by model inducers dexamethasone, omeprazole and rifampin was evaluated in primary cultured hepatocytes from man and laboratory animals. Inducer-specific species-differences were observed. Results with human hepatocytes from six human donors consistently show that both rifampin and dexamethasone were inducers of CYP3A activity (measured as testosterone 6beta-hydroxylase activity), with rifampin being more potent. Conversely, in rat hepatocytes, dexamethasone was a potent CYP3A inducer while rifampin was not an inducer. Rifampin but not dexamethasone induced CYP3A in minipig and beagle dog hepatocytes. Omeprazole was a potent inducer of CYP1A activity (measured as ethoxyresorufin-O-deethylase activity) in human, beagle dog and minipig hepatocytes, and not an inducer in rat hepatocytes. The species-differences observed suggest that human hepatocytes represent the most appropriate preclinical experimental system for the evaluation of P450 induction in human.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Animals
  • Cytochrome P-450 CYP1A1 / biosynthesis*
  • Cytochrome P-450 Enzyme System / biosynthesis*
  • Dexamethasone / pharmacology*
  • Dogs
  • Enzyme Induction
  • Female
  • Hepatocytes / drug effects*
  • Hepatocytes / enzymology*
  • Humans
  • Male
  • Middle Aged
  • Omeprazole / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Rifampin / pharmacology*
  • Species Specificity*
  • Swine, Miniature


  • Dexamethasone
  • Cytochrome P-450 Enzyme System
  • Cyp2c13 protein, rat
  • Cytochrome P-450 CYP1A1
  • Omeprazole
  • Rifampin