Effect of cimetidine on microsomal drug metabolism in man

The effect of cimetidine on human microsomal drug metabolism was studied. In five of six healthy volunteers therapeutic doses of cimetidine prolonged the half-life of antipyrine (range 12-37%; p < 0.05). Its clearance was decreased in five subjects (range 2-18%) and was increased in one subject (15%), the changes not being statistically significant. The volume of distribution increased on average by about 14% (range 9--19%; p < 0.001). Cimetidine in vitro inhibited the hydroxylation of benzo(a)pyrene and coumarin, as well as the O-deethylation of 7-ethoxycoumarin, by homogenised liver biopsies. The in vitro studies suggest that the effect of cimetidine on antipyrine elimination is due to inhibition of microsomal drug metabolism, which may prove an important drug interaction.