Time course of inhibition of gastric acid secretion by omeprazole and ranitidine in gastric fistula rats.
Basal, pentagastrin- and histamine-stimulated acid secretion were measured in gastric fistula rats treated with the H+/K(+)-ATPase inhibitor, omeprazole, and the H2-receptor antagonist, ranitidine. All doses of omeprazole (20, 30, 40, 80, 400 mumol/kg) and ranitidine (125, 187.5, 250, 375 mumol/kg) essentially abolished the basal acid output for various periods of time. Omeprazole, 80 mumol/kg, administered twice daily, reduced the 24-h basal acid secretion more effectively than did 400 mumol/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 mumol/kg) was more effective than ranitidine (125, 375 mumol/kg) in inhibiting acid secretion evoked by maximal doses of pentagastrin (650 nmol/kg per h) and histamine dihydrochloride (136 mumol/kg), whereas this difference was less pronounced for the inhibition of acid responses induced by a threshold dose (1.1 mumol/kg) of histamine. The inhibition evoked by omeprazole (80 mumol/kg x 2) and ranitidine (375 mumol/kg x 4) of basal and histamine (1.1 and 136 mumol/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.(ABSTRACT TRUNCATED AT 250 WORDS)
Seensalu
R
R
Department of Medicine, Huddinge University Hospital, Karolinska Institute, Sweden.
Girma
K
K
Romell
B
B
Nilsson
G
G
D000818:Animals; D005402:Fistula; D005744:Gastric Acid / Q000378:metabolism*; D005755:Gastrins / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009853:Omeprazole / Q000494:pharmacology*; D011899:Ranitidine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013270:Stomach / Q000502:physiology* / Q000601:surgery
D005755:Gastrins; D006632:Histamine; D011899:Ranitidine; D009853:Omeprazole