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%;=""><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="">
Key words cimetidine - microsomal drug metabolism - man - interaction - liver microsomes - antipyrine kinetics
Part of this work was presented at the Fall Meeting of the German Pharmacological Society, Munich, September 1979 (Puurunen et al. 1979)