Comparative metabolism of debrisoquine, 7-ethoxyresorufin and benzo(a)pyrene in liver microsomes from humans, and from rats treated with cytochrome P-450 inducers.

The metabolism of debrisoquine, 7-ethoxyresorufin and benzo(a)pyrene has been studied in human liver microsomes. There was a significant correlation (r = 0.70, P less than 0.05) between debrisoquine hydroxylation and 7-ethoxyresorufin 0-deethylation among various livers, and debrisoquine inhibited 7-ethoxyresorufin deethylation competitively. These results suggest that debrisoquine and 7-ethoxyresorufin may be metabolised by a common P-450 form in human liver. The effect of cytochrome P-450 inducers on the metabolism of the three substrates was also examined in rat liver. Debrisoquine hydroxylation was not enhanced by phenobarbitone, beta-naphthoflavone or isosafrole.