Comparative Metabolism of Debrisoquine, 7–Ethoxyresorufin and Benzo(a)pyrene in Liver Microsomes from Humans, and from Rats Treated with Cytochrome P–450 Inducers

Abstract
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 < 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 metabolized 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.