Effects of cimetidine and ranitidine on hepatic drug metabolism

Cimetidine has been shown to impair elimination of a number of drugs metabolized by the hepatic mixed-function oxidase enzymes. It is uncertain whether this is related to its histamine H2-receptor antagonism or to its intrinsic structure. Ranitidine is a more potent H2-receptor antagonist and has a completely different structure. Cimetidine (1 gm/day for 7 days) induced a 23% and 35% fall in mean systemic clearance of antipyrine and theophylline, whereas ranitidine (300 mg/day for 7 days) had no significant effect on the clearance of either drug. Our data suggest that the inhibition of drug metabolism by cimetidine is not related to histamine H2-receptor antagonism. Clinical Pharmacology and Therapeutics (1982) 31, 297–300; doi:10.1038/clpt.1982.36