Effect of acute and chronic cimetidine administration on acetaminophen metabolism in humans

In our study of the effect of acute cimetidine administration on acetaminophen metabolism, 10 healthy subjects were given an oral dose of acetaminophen (1 g) before and after administration of cimetidine (800 mg, po). In another experiment, 10 patients with duodenal ulcer received acetaminophen (1 g, po) before and after 2 months of cimetidine treatment (400 mg twice a day, po). Acetaminophen metabolism in blood and urine was studied for 9 h in each experiment. The half-life of acetaminophen was similar either in the absence or presence of both acute and chronic cimetidine administration. Although acute cimetidine ingestion did not affect acetaminophen urinary excretion, prolonged cimetidine treatment resulted in a slight but significant decrease of acetaminophen mercapturate urinary excretion. These findings suggest that, unlike acute cimetidine, prolonged histamine H₂ antagonist therapy inhibits acetaminophen oxidation to its reactive metabolite. The clinical relevance of such an interaction remains to be explored.