Effect of cimetidine or ranitidine pretreatment on hepatic mixed function oxidase activity in the rat

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Abstract

This study compared the effect of single equimolar oral doses of cimetidine (100 mg/kg) or ranitidine (139 mg/kg) on rat hepatic mixed function oxidases. Cimetidine significantly (p < 0.05) increased hexobarbital sleeping time and prolonged aminopyrine and theophylline elimination. In contrast, ranitidine did not significantly affect hexobarbital sleeping time and theophylline elimination but significantly (p < 0.025) increased aminopyrine elimination. Aminopyrine N-demethylase activity in vitro was significantly (p < 0.05) inhibited by cimetidine pretreatment but significantly (p < 0.025) increased by ranitidine pretreatment. The direct addition of cimetidine or SKF 525A to the 10,000g supernatant fraction from controlled liver homogenates decreased aminopyrine N-demethylase activity, whereas the direct addition of ranitidine tended to increase aminopyrine N-demethylase activity. A significant correlation (r = 0.65, p ≤ 0.005) was observed between hexobarbital sleeping time in vivo and aminopyrine N-demethylase activity in vitro in the same rat. The results of this study showed that cimetidine inhibited mixed function oxidases, whereas ranitidine had no effect or tended to stimulate mixed function oxidases.

Original languageEnglish (US)
Pages (from-to)580-584
Number of pages5
JournalDrug Metabolism and Disposition
Volume14
Issue number5
StatePublished - Dec 1 1986

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

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