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  • Title: [Comparison of the effects of cimetidine and ranitidine in vivo and in vitro on the hepatic microsomal enzyme system in rats].
    Author: Mavier P, Préaux AM, Delchier JC, Beauchant M, Dhumeaux D.
    Journal: Gastroenterol Clin Biol; 1983 Mar; 7(3):244-50. PubMed ID: 6303882.
    Abstract:
    Cimetidine, administered intraperitoneally to male rats (20 mg/kg and 40 mg/kg) induced a 125 p. 100 and 325 p. 100 increase in the hexobarbital sleeping time, respectively. Ranitidine, at the same dosage, had no effect. Cimetidine (40 mg/kg) decreased the aminopyrine metabolic clearance by 73 p. 100, whereas ranitidine caused no change. In vitro, cimetidine (1 mM) decreased 3 oxiding enzymatic activities, ethylmorphine demethylase, aniline hydroxylase and aminopyrine demethylase, measured in a 9,000 g supernatant fraction of rat liver, by 29 p. 100, 45 p. 100 and 73 p. 100, respectively. Ranitidine (1 mM) did not modify ethylmorphine and aminopyrine demethylase activities and induced a slight decrease of aniline hydroxylase activity (10 p. 100). Bilirubin and p-nitrophenol UDP-glucuronosyltransferase activities, measured on the microsomal fraction, were slightly inhibited (5 p. 100 and 4 p. 100, respectively) by cimetidine (1 mM). Ranitidine (1 mM) did not change these enzymatic activities. The effects of cimetidine and ranitidine on both the oxidizing and conjugating enzymatic activities were not notably affected by pretreatment with phenobarbital (100 mg/kg, intraperitoneally for 3 days). These results point out that: 1) in vivo and in vitro, ranitidine, in contrast with cimetidine, does not inhibit the microsomal drug-oxidizing system; 2) neither ranitidine nor cimetidine decrease the activity of the microsomal drug-conjugating system. They clearly explain why cimetidine interferes with the disposition of drugs oxidized but not of drugs conjugated by the liver.
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