Fig. 4.

Effects of various P450 isoform-selective inhibitors on the formation of 2-hydroxymetronidazole by pooled human liver microsomes. Pooled human liver microsomes were incubated with metronidazole (100 μM) in the presence or absence of various selective, chemical inhibitors, with the major P450 inhibited enclosed in parentheses. Incubations were conducted as described under Materials and Methods. The upper panel shows the effects of selective, competitive P450 inhibitors, whereas the lower panel shows the effects of mechanism-based inhibitors on formation of 2-hydroxymetronidazole. Incubations containing mechanism-based inhibitors were preincubated with human liver microsomes and NADPH-generating system for 20 minutes prior to initiating the reaction with substrate. Each bar represents the mean of duplicate determinations.