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  • Title: Cimetidine: a specific inhibitor of hepatic aryl hydrocarbon hydroxylase (AHH) in the rat.
    Author: Drew R, Rowell J, Grygiel JJ.
    Journal: Res Commun Chem Pathol Pharmacol; 1981 Jul; 33(1):81-93. PubMed ID: 7268211.
    Abstract:
    Aryl hydrocarbon hydroxylase was selectively inhibited in hepatic microsomes prepared 2 hours after administration of cimetidine (150 mg/kg, i.p.) to male Wistar rats. Cytochrome P-450 content and other mixed function oxidase activities were not affected. In rats pretreated with phenobarbital or 3-methylcholanthrene, cimetidine caused a 50% and 90% reduction or aryl hydrocarbon hydroxylase activity respectively, compared to 70% inhibition in uninduced animals. Chronic administration of cimetidine (150 mg/kg, b.i.d. for 5 days) to uninduced rats resulted in 70% inhibition of aryl hydrocarbon hydroxylase but no change in other microsomal enzyme activities. Hexobarbital sleeping time was markedly prolonged 30 min after a single dose of cimetidine but had returned to control values after 24 hrs. Similar effects were observed with chronic dosing of cimetidine. It is concluded that in vivo administration of cimetidine is a relatively specific inhibitor of hepatic aryl hydrocarbon hydroxylase in the rat, and that cimetidine does not induce the microsomal mixed function oxidase system when administered chronically.
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