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 6β-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.
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