Res Vet Sci. 1990 Nov;49(3):279-82.
Effects of cimetidine and ranitidine on basal gastric pH, free and total acid content in pigs.

Sangiah S, Amouzadeh HR, Barron S, Maxwell C, Mauromoustakos A.

Department of Physiological Sciences, Oklahoma State University, Stillwater 74078.

The effects of intramuscular administration of multiple doses of cimetidine and ranitidine on basal gastric pH, free and total acid content from young adult pigs were studied. Cimetidine (4.5 mg kg-1, four times a day, intramuscularly, for three days) significantly (P less than 0.05) raised the basal gastric pH above 3.5 with a simultaneous reduction in free acid content at two, three and 26 hours after the administration of the eighth dose. Ranitidine (0.75 mg kg-1, four times a day, intramuscularly, for three days) significantly (P less than 0.05) raised the basal gastric pH above 3.5 with a concomitant reduction in free acid content at three and 38 hours after the administration of the eight dose. Neither cimetidine nor ranitidine had any significant effects on total acid content. These results confirm that the pig is a basal acid secretor and that the pharmacodynamics and pharmacokinetics of cimetidine and ranitidine in pigs might be different from those in humans.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2267416&dopt=Abstract ranitidine






Z Gastroenterol. 1990 Aug;28(8):379-82.
Combined effect of pirenzepine and ranitidine on the nocturnal intragastric pH in non-responders to ranitidine.

Walker S, Klotz U, Bode JC.

Department of Gastroenterology, Robert-Bosch-Krankenhaus, Stuttgart, FRG.

Both H2-receptor antagonists and pirenzepine are used in the treatment of peptic ulcer disease. Since we have recently found a higher frequency of non-responders to H2-receptor antagonists among cirrhotics, we tested the effect of the combination of 50 mg pirenzepine and 300 mg ranitidine in 25 patients (12 cirrhotics and 13 controls) in whom a normal 300 mg dose of ranitidine had failed to suppress intragastric acidity. Nocturnal intragastric pH was continuously monitored for 12 hours. A rise in the intragastric pH above 4.0 for more than 6 hours following the oral dose at 18.00 h was considered as response. In all subjects, plasma concentrations of ranitidine and pirenzepine were in the therapeutic range. Coadministration of pirenzepine and ranitidine resulted in sufficient increase of the intragastric pH in only 4 of the 12 patients with cirrhosis, and in 4 of the 13 control patients. This treatment failure in most of our patients does not support the view that excessive vagal drive might play an important role in the non-response to H2-blockers. With regard to the benefit resulting from coadministration of pirenzepine and ranitidine, there seems to be no difference between cirrhotic and control patients.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2275257&dopt=Abstract ranitidine






Scand J Gastroenterol Suppl. 1990;178:72-8.
Maintenance therapy of duodenal and gastric ulcer with H2-receptor antagonists.

Boyd EJ, Penston JG, Wormsley KG.

Ninewells Hospital and Medical School, Dundee, Scotland.

Maintenance therapy with either ranitidine or cimetidine has been administered for up to 5 years to several hundred patients suffering from duodenal or gastric ulcer disease. Maintenance treatment prevented symptomatic ulcer relapse in approximately three-quarters of patients over this period of time. About half of symptomatic ulcer relapses occurred during the 1st year of maintenance therapy, and thereafter the symptomatic recurrence rate was extremely low. Potentially the most important effect of maintenance therapy was to reduce the incidence of ulcer complications, particularly haemorrhage (from 6.2% to 0.4% during the 1st year of duodenal ulcer maintenance). Maintenance therapy is therefore likely to reduce ulcer morbidity and to be cost-beneficial in patients who have previously experienced an ulcer complication and are at an increased risk of the same complication in the future. Maintenance therapy with 300 mg ranitidine daily was more effective than 150 mg ranitidine at night in smokers and may be a useful therapeutic option for smokers who relapse during maintenance therapy with 150 mg ranitidine at night or for smokers in whom it is mandatory to prevent ulcer recurrence because of a previous complication. Asymptomatic ulcers occurring during maintenance therapy are clinically benign, and rehealing such ulcers does not alter the subsequent clinical course. Point prevalences of asymptomatic reulceration should not be used when assessing the clinical value of maintenance therapy.

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Gastroenterology. 1990 Mar;98(3):654-61.
Gastric acid hypersecretion in refractory gastroesophageal reflux disease.

Collen MJ, Lewis JH, Benjamin SB.

Department of Medicine, Georgetown University Medical Center, Washington, D.C.

We prospectively evaluated gastric acid output (mEq/h), gastric volume output (ml/h), ambulatory 24-h esophageal pH monitoring, and the endoscopic appearance of the esophagus in 23 patients undergoing treatment of chronic long-standing pyrosis. Twelve of these 23 individuals (52%) remained symptomatic after 3 mo of standard antisecretory treatment with ranitidine, 150 mg twice daily. When compared with initial responders, those patients who did not experience complete symptomatic relief on therapy had significantly higher basal acid output (p less than 0.001), basal volume output (p less than 0.02), and basal upright (but not supine) reflux time (p less than 0.05). Nine of the 12 patients who did not respond to initial treatment had gastric acid hypersecretion (basal acid output greater than 10 mEq/h), and 10 of the 12 had Barrett's epithelium compared with only 1 patient in the initial-responder group (p less than 0.001). All 12 nonresponders were treated for an additional 3 mo with increased doses of ranitidine (mean, 1280 mg/day; range, 600-1800 mg/day), and complete disappearance of pyrosis occurred in 10 of the 12, although no significant endoscopic regression was observed in the extent of the underlying columnar mucosa in those with Barrett's esophagus over the 6-mo duration of the study. A significant correlation was shown between the daily ranitidine dose required to eliminate symptoms and the pretreatment basal acid output (r = 0.81, p less than 0.001); gastric acid output had to be almost totally suppressed (i.e., less than 1 mEq/h) for pyrosis to disappear completely. No side effects occurred with any of these high doses of ranitidine. We conclude that a subgroup of patients with long-standing symptomatic gastroesophageal reflux disease who do not respond




Dig Dis Sci. 1990 Mar;35(3):385-91.
Effect of ranitidine on acetaminophen-induced hepatotoxicity in dogs.

Panella C, Makowka L, Barone M, Polimeno L, Rizzi S, Demetris J, Bell S, Guglielmi FW, Prelich JG, Van Thiel DH, et al.

Department of Gastroenterology, University of Bari, Italy.

The effect of ranitidine administration upon the hepatotoxic effect produced by a multidose acetaminophen administration regimen was examined. Seventy-two dogs received three subcutaneous injections of acetaminophen (750, 200, 200 mg/kg body wt) in DMSO (600 mg/ml) at time zero, 9 hr later, and 24 hr after the first dose. Ten control animals (group I) were not given ranitidine, the remaining 62 dogs received an intramuscular injection of ranitidine 30 min before each acetaminophen dose. Three different doses of ranitidine were used (mg/kg body wt): 50 mg, group II (33 dogs); 75 mg, group III (14 dogs); 120 mg, group IV (15 dogs). Ranitidine reduced the expected acetaminophen-induced hepatoxicity in a dose-response manner. Moreover, a significant correlation was found between the ranitidine dose and the survival rate, as evidenced by transaminase levels in the serum and histology of the liver. This model of fulminant hepatic failure induced by acetaminophen and its modulation with ranitidine provides clinical investigators with a research tool that will be useful in the future investigation of putative medical and surgical therapies being investigated for use in the clinical management of fulminant hepatic failure. Because of the size of the animal used in this model, frequent and serial analyses of blood and liver were available for study to determine the effect of therapy within a given animal as opposed to within groups of animals.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2307085&dopt=Abstract ranitidine






Regul Pept. 1990 Mar 27;28(1):107-18.
Evidence that gastrin enhances 45Ca uptake into bone through release of a gastric hormone.

Hakanson R, Persson P, Axelson J, Johnell O, Sundler F.

Department of Pharmacology, University of Lund, Sweden.

An acute challenge with gastrin-17 enhanced the uptake of 45Ca into sternum and several long bones in rats by about 10-30%; gastrectomy prevented this effect. Long-term treatment with (Leu15)-gastrin-17 (continuous infusion via osmotic minipumps for 4 weeks) enhanced the uptake of 45Ca into bone (examplified by radius and sternum) by 18-26% (tested on the last day of the infusion). Surgical removal of the acid-producing part of the stomach (fundectomy) or treatment with the anti-ulcer drugs, ranitidine (a histamine H2-receptor antagonist administered by continuous infusion) or omeprazole (an H+/K(+)-ATPase inhibitor administered daily by gastric tube for 4 weeks), induced sustained hypergastrinemia (through loss of acid feedback inhibition of gastrin release). The ranitidine- and omeprazole-evoked hypergastrinemia was associated with 32-62% enhancement of bone 45Ca uptake but the hypergastrinemia of fundectomized rats was not. Gastrectomy abolished the effect of omeprazole. We suggest that exogenous and endogenous gastrin influences calcium uptake into bone indirectly by releasing a calciotropic hormone (gastrocalcin) from the acid-producing part of the stomach. The bone ash weight was reduced by gastrectomy or fundectomy (4 weeks), but neither ranitidine nor omeprazole-evoked hypergastrinemia (4 weeks) raised the bone ash weight. The stimulated calcium uptake into bone of hypergastrinemic rats treated with ranitidine or omeprazole was associated with a 22-32% increase in the density of osteoclasts in the tibia. This finding is in line with the hypothesis that long-lasting hypergastrocalcinemia produces accelerated turn-over of bone rather than increased bone calcium content.

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Int J Tissue React. 1990;12(5):299-307.
Bombesin-induced pancreatic secretion and growth in rats: effect of proglumide, spantide and ranitidine.

Scarpignato C, Varga G, Dobronyi I, Papp M.

Institute of Pharmacology, School of Medicine and Dentistry, University of Parma, Italy.

The effect of proglumide (400 mg/kg), spantide (400 g/kg) and ranitidine (20 mg/kg) on pancreatic secretory and trophic response to bombesin (10 micrograms/kg) was studied in the rat. Drugs were administered alone or combined with bombesin three times daily for 5 days. Saline-treated rats were used as controls. At the end of treatment, animals were anaesthetized and pancreatic juice was collected for 1 h after caerulein stimulation (1 microgram/kg intraperitoneally). Afterwards, rats were sacrificed and the weight and composition of pancreatic tissue were determined. As compared with control (saline) values, the volume of pancreatic juice and the output of trypsin and amylase were increased by treatment with bombesin. Neither proglumide nor spantide affected basal and caerulein-stimulated pancreatic exocrine secretion. Ranitidine, although unable to modify protein and enzyme content of pancreatic secretion, significantly reduced the volume of pancreatic juice in both basal conditions and after caerulein stimulation. Bombesin increased pancreatic weight as well as the protein and enzymatic contents of the gland. Neither the weight of the pancreas nor its composition were significantly affected by CCK-antagonist proglumide, the putative bombesin antagonist spantide or the H2-receptor antagonist ranitidine. These results show that bombesin has a trophic effect on rat pancreas and concomitantly increases its secretory capacity. Both effects are likely to be mediated through a direct action of the peptide on the pancreatic gland.

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Eur J Pharmacol. 1990 May 3;180(1):145-52.
Time course of inhibition of gastric acid secretion by omeprazole and ranitidine in gastric fistula rats.

Seensalu R, Girma K, Romell B, Nilsson G.

Department of Medicine, Huddinge University Hospital, Karolinska Institute, Sweden.

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)

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Am J Hosp Pharm. 1990 Jun;47(6):1346-9.
Pharmacist intervention program focused on i.v. ranitidine therapy.

Santora J, Kitrenos JG, Green ER.

Erie County Medical Center, Buffalo, NY.

A staff pharmacist intervention program designed to modify inappropriate dosage intervals for i.v. ranitidine and promote timely conversion to oral therapy is described. Records of patients who were receiving i.v. ranitidine were reviewed for eight weeks to determine whether the dosage interval was appropriate and whether they began receiving oral ranitidine within 24 hours of an order for an oral diet or other oral medications. Pharmacists were then asked to determine the proper i.v. ranitidine dosage interval based on creatinine clearance and the oral dosage that would be appropriate when i.v. therapy was no longer indicated. The information was used to complete an intervention form that was placed in the patient's chart. During the baseline phase the i.v. dosage interval was inappropriate for 49 of 139 patients; 617 i.v. doses costing $4214 were administered to 62 patients for whom oral therapy was indicated; conversion to oral therapy occurred appropriately for 39 of 68 patients (57%). In the intervention phase 138 patients received i.v. ranitidine. Pharmacists made 51 recommendations for adjusting the i.v. dosage interval, and 18 were implemented within 24 hours. All six recommendations to convert immediately to oral therapy were also implemented within 24 hours. A total of 280 inappropriate i.v. doses costing $1912 were given to 30 patients for whom oral therapy was indicated. Conversion to oral therapy occurred appropriately for 53 of 76 patients (70%). A simple program of monitoring and intervention by staff pharmacists when i.v. ranitidine therapy is begun can save money and promote the appropriate use of this drug.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2368729&dopt=Abstract ranitidine