Comparison of the Effects of Feprazone and Phenylbutazone on Testosterone Hydroxylations in Mouse Hepatic Microsomes

Abstract

The inhibitory and inducing actions of feprazone (FZ), an anti-inflammatory agent, on testosterone hydroxylations in the mouse hepatic microsomal mixed-function oxidase system were compared with those of phenylbutazone (PZ).As regards inhibitory effects, testosterone hydroxylations were competitively inhibited by addition of FZ and PZ in vitro. No significant difference was found between FZ and PZ in inhibitory potency for 6β- and for 16α-hydroxylations, but the inhibitory effect FZ on 7α-hydroxylation was stronger than that of PZ. However, the three hydroxylations were noncompetitively inhibited in microsomes from mice treated with each agent.As regards the inducing action, only 6β-hydroxylase activity was increased following continuous administration of low doses (75 mg/kg) of FZ and of PZ; in addition, 16α-hydroxylase activity was also increased following continuous administration of high doses (150 mg/kg) of these drugs. 7α-Hydroxylase activity, however, was not significantly affected by either low or high doses. We also found that the patterns and the extents of induction of the three hydroxylase activities by FZ and PZ were different from those by phenobarbital or β-naphthoflavone.These results indicate that FZ and PZ have essentially identical inducing effects, whereas FZ exhibits a greater inhibitory effect than PZ on the activity of certain P-450 isozymes such as 7α-hydroxylase in the mouse mixed-function oxidase system.