Comparative pharmacodynamics and pharmacokinetics of cimetidine and ranitidine

Ranitidine and cimetidine are competitive antagonists of histamine at H2-receptor sites in the gastric mucosa. Both drugs reduce output of basal and stimulated gastric acid and pepsin secretion in normal healthy subjects and duodenal ulcer patients. Pharmacodynamic and pharmacokinetic differences exist between the drugs, some of which are of clinical significance. Ranitidine is a 6-8 times more potent inhibitor of gastric secretions and also causes a greater reduction in intragastric acidity of nocturnal secretions after usual therapeutic doses. Absorption from the gastrointestinal tract of both drugs is good, with peak plasma concentration occurring approximately 90 minutes after oral administration. Systemic bioavailability is approximately 70% with cimetidine and 50% with ranitidine. Both drugs demonstrate biexponential elimination curves from the plasma after intravenous administration and a bimodal curve after oral administration which is probably the result of enterohepatic recirculation. The elimination half-lives of cimetidine and ranitidine are 1.7-2.1 hours and 2.1-3.1 hours, respectively, with apparent volumes of distribution approximating 50L and 75L, respectively. Both drugs are eliminated, largely unchanged, via the kidneys. Major differences between these agents are found in cimetidine's biological activity at sites other than the gastric H2-receptors. These include: antiandrogenic effects with the appearance of feminizing characteristics in men, especially with large doses, like those used to treat Zollinger-Ellison syndrome; interference with the hepatic P-450 mixed-function oxidase enzyme system, which results in drug interactions with warfarin, phenytoin, theophylline and other drugs; and central nervous system effects characterized by confusion, particularly in elderly patients and those with renal failure. Such side effects have not been directly related to ranitidine treatment and substitution of ranitidine for cimetidine has reportedly provided effective alternative treatment in patients intolerant to cimetidine.