The effects of 1-alkylimidazoles on hepatic drug-metabolizing enzyme activity

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Abstract
1. Certain 1 -alkylimidazoles, containing a C8-C15 alkyl group, are potent inhibitors of liver microsomal drug oxidations. At a concentration of 10−4M, they inhibited almost entirely the aminopyrine demethylase activity of rat liver 10 000 g supernatant fraction. In vivo, they prolonged hexobarbitone sleeping time in mice. 2. Inhibition of aminopyrine demethylase by 1-geranylimidazole was of a mixed type at high inhibitor concentrations and noncompetitive at low concentrations. 3. Addition of 1-geranylimidazole to rat liver microsomal fraction elicited a type II spectral change, but the use of hexobarbitone as a modifier revealed both type I and type II components. 4. Rats killed 24 h after the last of eight daily (100 mg/kg) doses of 1-do-decylimidazole showed marked induction of aminopyrine demethylase and aniline hydroxylase activities, but no change in cytochrome P-450 level.