Inhibition of microsomal drug metabolism by histamine H2-receptor antagonists studied in vivo and in vitro in rodents

K. V. Speeg, R. V. Patwardhan, G. R. Avant, M. G. Mitchell, S. Schenker

Research output: Contribution to journalArticlepeer-review

112 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)89-96
Number of pages8
Issue number1
StatePublished - Jan 1982
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology


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