title: 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.
abstract: 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.
authors.affiliation: In Vitro Technologies Inc., 1450 South Rolling Road, Baltimore, MD 20227, USA.
authors.forename: C
authors.initials: C
authors.lastname: Lu
authors.forename: A P
authors.initials: AP
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D003907:Dexamethasone / Q000494:pharmacology*; D004285:Dogs; D004790:Enzyme Induction; D005260:Female; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012293:Rifampin / Q000494:pharmacology*; D013045:Species Specificity; D013556:Swine, Miniature
chemical_list: D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; C113764:Cyp2c13 protein, rat; D019363:Cytochrome P-450 CYP1A1; D009853:Omeprazole; D012293:Rifampin