Bufuralol 1'-hydroxylase activity of the rat. Strain differences and the effects of inhibitors.

The kinetics of bufuralol 1'-hydroxylase activity of hepatic microsomal fractions have been determined in female DA and Fischer 344 rats, strains between which there is a large difference in debrisoquine 4-hydroxylase activity. Two components of bufuralol 1'-hydroxylase activity could be observed in both strains. Although there were differences between the strains in Vmax and Km of both components of activity, these were much less marked than the differences previously reported for debrisoquine 4-hydroxylase (Kahn et al., Drug Metab. Dispos. 13, 510 (1985)). The kinetics of bufuralol 1'-hydroxylase activity were such that the difference in activity between the strains varied with the concentration of bufuralol, 4-5-fold at 2.5 microM, no difference at 100 microM Competitive inhibitors of debrisoquine 4-hydroxylase activity in man were competitive inhibitors of bufuralol 1'-hydroxylase activity in the Fischer 344 rat, but not in the DA rat. The Ki for inhibition of bufuralol 1'-hydroxylase activity by debrisoquine in the Fischer 344 rat was 184 microM, compared with a Km for the 4-hydroxylation of this compound of 10.5 microM. It is concluded that the major isozyme of cytochrome P-450 catalysing the 1'-hydroxylation of bufuralol in the rat is different from that catalysing debrisoquine 4-hydroxylation (P-450UT-H).