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  • Title: Inhibition of microsomal drug metabolism by histamine H2-receptor antagonists studied in vivo and in vitro in rodents.
    Author: Speeg KV, Patwardhan RV, Avant GR, Mitchell MC, Schenker S.
    Journal: Gastroenterology; 1982 Jan; 82(1):89-96. PubMed ID: 6118315.
    Abstract:
    Cimetidine has been demonstrated to impair microsomal oxidative drug metabolism in a dose-dependent manner in an animal model. The inhibition has also been shown to be rapid, occurring after a single dose. In the present study we demonstrate that recovery from inhibition after cimetidine withdrawal is also rapid, occurring within 24 h. Furthermore, chronic dosing with cimetidine does not result in tolerance to the inhibitory effect. Other H2-antihistamines have also been studied both in vivo and in vitro. Based on spectral binding changes, in vitro enzyme assays and in vivo aminopyrine breath tests, ICI 125,211, ranitidine, and cimetidine sulfoxide are much less inhibitory than cimetidine. The ability of cimetidine to impair the elimination of aminopyrine in the mouse after acute liver damage was greater than in the normal mouse.
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