Effect of cimetidine on histamine- and pentagastrin-stimulated gastric secretion in healthy subjects.

Cimetidine-induced inhibition of gastric acid and pepsin secretion in response to histamine and pentagastrin simulation was studied in four healthy young subjects. Different doses of histamine and pentagastrin were administered alone and in combination with cimetidine on separate days; the order of administration was randomized. As the dose of histamine increased, the inhibitory effect of 0.6mg.kg-1h-1 of cimetidine on acid output decreased. With supramaximal histamine stimulation the inhibition was completely overcome. These results are consistent with competitive inhibition of histamine-stimulated acid output by cimetidine in man. After pentagastrin stimulation inhibition of acid output by cimetidine could not be overcome by increasing the dose of the stimulant, suggesting a noncompetitive inhibition of pentagastrin-evoked acid output. It is concluded that the kinetics of cimetidine-induced inhibition of histamine- and pentastrin-stimulated gastric acid output are different. At approximately half maximal stimulation of acid secretion, cimetidine was a more potent inhibitor of histamine than of pentagastrin. Pepsin output in response to both histamine and pentagastrin stimulation was also inhibited by cimetidine.