Time course of inhibition of gastric acid secretion by omeprazole and ranitidine in gastric fistula rats

Abstract

Basal, pentagastrin- and histamine-stimulated acid secretion were measured in gastric fistula rats treated with the H +/K +-ATPase inhibitor, omeprazole, and the H 2-receptor antagonist, ranitidine. All doses of omoprazole (20, 30, 40, 80, 400 μmol/kg) and ranitidine (125, 187.5, 250, 375 μmol/kg) essentially abolished the basal acid output for various periods of time. Omeprazole, 80 μmol/kg, administered twice daily, reduced the 24-h basal acid secretion more effectively than did 400 μmol/kg given once daily. Four daily administrations of ranitidine reduced the 24-h basal acid output to a similar extent as omeprazole administered twice. Omeprazole (20, 80 μmol/kg) was more effective than ranitidine (125, 375 μmol/kg) in inhibiting acid secretion evoked by maximal doses of pentagastrin (650 nmol/kg per h) and histamine dihydrochloride (136 μmol/kg), whereas this difference was less pronounced for the inhibition of acid responses induced by a threshold dose (1.1 μmol/kg) of histamine. The inhibition evoked by omeprazole (80 μmol/kg × 2) and ranitidine (375 μmol/kg × 4) of basal and histamine (1.1 and 136 μmol/kg)-induced acid secretion was similar after 1 and 4 weeks of treatment. After the end of drug administration, the acid secretion induced by threshold doses of histamine was significantly elevated in the omeprazole-treated rats, whereas no significant hypersecretion of acid was seen during the recovery period in rats treated with ranitidine. Plasma gastrin concentrations were significantly elevated after 4 weeks of treatment with omeprazole but returned to pretreatment levels after 4 weeks of recovery. Ranitidine and the vehicle, hydroxypropylmethylcellulose, did not significantly change the plasma gastrin concentration.