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

Induction of P450 isoforms 1A (CYP1A) and 3A (CYP3A) by model inducers dexa methasone, omeprazole and rifampin was evaluated in primary cultured hepato cytes from man and laboratory animals. Inducer-specific species-differences were observed. Results with human hepatocytes from six human donors consis tently show that both rifampin and dexamethasone were inducers of CYP3A act ivity (measured as testosterone 6 beta -hydroxylase activity), with rifampi n being more potent. Conversely, in rat hepatocytes, dexamethasone was a po tent CYP3A inducer while rifampin was not an inducer. Rifampin but not dexa methasone induced CYP3A in minipig and beagle dog hepatocytes. Omeprazole w as a potent inducer of CYP1A activity (measured as ethoxyresorufin-O-deethy lase activity) in human, beagle dog and minipig hepatocytes, and not an ind ucer in rat hepatocytes. The species-differences observed suggest that huma n hepatocytes represent the most appropriate preclinical experimental syste m for the evaluation of P450 induction in human. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.