Effect of Cimetidine on Pentagastrin-stimulated Gastric Secretion in Healthy Man

Two series of experiments were carried out in three healthy volunteers. In one series increasing doses of cimetidine were tested on a constant background stimulation with 0.15 microgram-kg-1h-1 of pentagastrin. In the other series of experiments increasing doses of pentagastrin were given either alone or in combination with a fixed dose of cimetidine (1.2 mg-kg-1h-1). Pentagastrin and cimetidine were given as continuous intravenous infusions, the various doses tested on separate days. The inhibition of acid output in response to pentagastrin stimulation increased almost linearly with the log dose of cimetidine. Fifty per cent inhibition of the response to 0.15 microgram-kg-1h-1 of pentagastrin was achieved by about 0.6 mg-kg-1h-1 of cimetidine. 2.4 mg-kg-1h-1 of cimetidine gave on average 90% inhibition. The inhibition caused by cimetidine decreased to a minimum of 57% and could not be overcome by increasing the doses of pentagastrin. The results suggest a mixture of competitive and noncompetitive interaction. The effect of cimetidine on pepsin secretion was less regular. Generally, pepsin output was less inhibited than acid output.