Cimetidine plasma concentration‐response relationships

Cimetidine plasma concentration-response relationships were investigated in six healthy subjects using suppression of gastric acid secretion under continuous pentagastrin stimulation (1.5 µg/kg/hr) as a test model. With the Hill equation the sigmoid was preferable to the linear relationship between plasma concentration and effect, and there were significant correlations with p values under 0.01 in all but one subject. From the individual curves a mean plasma level of 0.78 µg/ml (range 0.54 to 1.04 µg/ml) for 50% inhibition of gastric acid secretion was determined; mean concentration for 90% inhibition was calculated to be 3.9 µg/ml. The model described should allow determination of whether different patient populations (e.g., healthy subjects, patients with ulcers, male and female patients, patients with renal or liver disease) differ from one another in concentration-response relationships to histamine H2-receptor antagonists, so that appropriate drug plasma levels should be achieved for specific degrees of inhibition of gastric acid secretion. Clinical Pharmacology and Therapeutics (1981) 29, 744–748; doi:10.1038/clpt.1981.105