Aliment Pharmacol Ther. 1987 Oct;1(5):369-81.
Ranitidine and cimetidine in the healing of duodenal ulcer: meta-analysis of comparative clinical trials.

McIsaac RL, McCanless I, Summers K, Wood JR.

Department of Gastroenterology, Glaxo Group Research Ltd, Greenford, UK.

All available ranitidine and cimetidine comparative trials in acute duodenal ulcer disease were examined: of the 44 trials, 36 favoured ranitidine, and there was an overall difference in ulcer healing of 7%. Further stratification enabled examination of trials with common attributes: the most frequent endoscopic assessment was at 4 weeks to compare ranitidine 150 mg twice daily with cimetidine 1 g day-1 or 400 mg b.d. Twenty of these trials had sufficient data to permit pooling. Ranitidine was favoured in 18/20 trials and in three the differences achieved statistical significance. Results of the trials were combined using meta-analysis to calculate differences in ulcer healing. Most studies had sample sizes that were insufficient to detect clinically-important differences; the power to detect a 20% difference was less than 80% in 15/20 trials, and for a 10% difference was less than 80% in all but one trial. Fifteen trials compared ranitidine 150 mg b.d. with cimetidine 1 g day-1: healing after 4 weeks therapy was overall 6% greater for ranitidine. This was statistically significant (P less than 0.05) and the combined total number of patients had a power of 83% to detect this difference. In five trials the dose of cimetidine used was 400 mg b.d.: the 12% difference in healing in favour of ranitidine 150 mg b.d. was statistically significant, and the combined trials had a power of 95% to detect this difference. Ranitidine 150 mg twice daily heals significantly more duodenal ulcers after 4 weeks of therapy than either cimetidine 400 mg b.d. or cimetidine 1 g day-1.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2980967&dopt=Abstract ranitidine






Life Sci. 1986 Jan 13;38(2):173-82.
Ranitidine potentiates ileum contractions caused by GABA and electrical stimulation.

Trzeciakowski JP, Cole S.

GABA-evoked contractions of the guinea pig ileum were significantly potentiated by the histamine H2-receptor antagonist ranitidine in concentrations above 10 microM. To help define the mechanism of this interaction, the present study compared the effects of ranitidine on contractile responses of the guinea pig ileum to GABA, acetylcholine (A Ch) and electrical stimulation of intrinsic cholinergic neurons. Ranitidine, at concentrations that potentiated responses to GABA, also potentiated contractions induced by transmural electrical stimulation. The ability of ranitidine to amplify these latter responses was antagonized by atropine. Contractile responses to exogenous A Ch, however, were unaffected by ranitidine at any concentration. These results suggest that prejunctional, rather than postjunctional mechanisms, are of primary importance in the interaction between ranitidine and GABA.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3003475&dopt=Abstract ranitidine






Gut. 1986 Oct;27(10):1143-6.
Dose related in vitro effects of ranitidine and cimetidine on basal and ACTH-stimulated steroidogenesis.

Kenyon CJ, Fraser R, Birnie GG, Connell JM, Lever AF.

Isolated bovine adrenocortical cells were incubated with and without 3 ng/ml ACTH, with various concentrations (10-1000 micrograms/ml) of either cimetidine or ranitidine. Cortisol, corticosterone, and deoxycorticosterone outputs were measured. Cimetidine and ranitidine at 320 and 1000 micrograms/ml inhibited ACTH-stimulated corticosterone and cortisol synthesis and cimetidine decreased basal cortisol synthesis. The inhibitory effects of cimetidine on cortisol synthesis were approximately 10 times greater than those of ranitidine. Cimetidine (1000 micrograms/ml), but not ranitidine increased deoxycorticosterone synthesis by ACTH-stimulated cells, indicating inhibition of 11 beta-hydroxylation in the adrenal steroidogenic pathway. Although doses of cimetidine and ranitidine which produce these in vitro effects are much greater than plasma concentrations in normal clinical use, they might be important in acutely ill patients given intravenous bolus injections of cimetidine, or if either antagonist were accumulated by the adrenal to produce high intracellular concentrations.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3023203&dopt=Abstract ranitidine






Anaesthesia. 1986 Dec;41(12):1202-6.
Combination treatment with ranitidine and sodium bicarbonate prior to obstetric anaesthesia.

Mathews HM, Wilson CM, Thompson EM, Moore J.

The gastric pH and volume were measured in 175 patients undergoing elective, and 313 undergoing emergency, obstetric procedures. Ranitidine 150 mg was administered orally every 6 hours in labour and at least 2 hours before elective Caesarean section. Patients received 20 ml of 8.4% sodium bicarbonate orally immediately prior to induction of anaesthesia. The combination of ranitidine and sodium bicarbonate produced marked alkalinisation of gastric contents (mean pH 8.9). The administration of sodium bicarbonate pre-operatively in patients who received ranitidine less than 2 hours before operation led to satisfactory elevation of gastric pH. Only four patients had a gastric pH less than 2.5, one patient refused any medication, two received only ranitidine and one patient had a long interval from administration of bicarbonate to aspiration of gastric contents. Gastric volumes were high in labouring patients (mean 84 ml) despite administration of ranitidine. The effectiveness of sodium bicarbonate as a single dose antacid therapy prior to obstetric anaesthesia requires further study.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3028202&dopt=Abstract ranitidine






Cancer Treat Rep. 1986 Dec;70(12):1443-5.
Effect of cimetidine and ranitidine on the metabolism and toxicity of hexamethylmelamine.

Hande K, Combs G, Swingle R, Combs GL, Anthony L.

In a rat model, doses of 20-120 mg/kg of cimetidine prolonged in a dose-related manner the half-life of hexamethylmelamine by 29%-80%, while doses of 1-25 mg/kg of ranitidine did not. Administration of 120 mg/kg of cimetidine with a single 350-mg/kg dose of hexamethylmelamine increased toxicity from LD30 to LD75 (P = 0.005). When combined with 25 mg/kg of ranitidine, a statistically insignificant (P = 0.16) 15% increase in hexamethylmelamine toxicity was noted. These studies indicate that cimetidine but not ranitidine increases the toxicity of hexamethylmelamine through inhibition of microsomal metabolism.

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Gastroenterology. 1986 Feb;90(2):391-9.
Plasma gastrin and gastric enterochromaffinlike cell activation and proliferation. Studies with omeprazole and ranitidine in intact and antrectomized rats.

Larsson H, Carlsson E, Mattsson H, Lundell L, Sundler F, Sundell G, Wallmark B, Watanabe T, Hakanson R.

Unoperated female rats were subjected to daily oral treatment with omeprazole (10 or 400 mumol/kg body wt), ranitidine (175 + 175 + 350 mumol/kg body wt), or vehicle and antrectomized rats were treated with omeprazole (400 mumol/kg body wt) or vehicle. After 10 wk of treatment, plasma gastrin levels were high in unoperated rats treated with the high omeprazole dose and with ranitidine, and low in antrectomized controls. Plasma gastrin levels were slightly higher in the low-dose omeprazole group than in the intact controls. In antrectomized rats treated with the high dose of omeprazole, the plasma gastrin level was in the same range as in intact control rats. A close correlation (r = 0.89, p less than 0.0001) was found between the plasma gastrin level and the oxyntic mucosal enterochromaffinlike cell density (as well as the tissue levels of histidine decarboxylase and histamine in the oxyntic mucosa) in all groups. The somatostatin cell density in the oxyntic mucosa was not altered by the various treatments. During a recovery period of 10 wk after the 10-wk treatment, the enterochromaffinlike cell density and histamine concentration decreased by 30%-40% in the rats treated with the high dose of omeprazole, whereas the corresponding values increased by 50% and 40%, respectively, in the control rats. The difference between the two groups, however, was still statistically significant. Plasma gastrin levels and gastric histidine decarboxylase activity returned to control values during recovery. The results suggest that the observed changes in enterochromaffinlike cell density are related to the plasma gastrin levels and that they are reversible. it is concluded that neither omeprazole nor ranitidine per se i




J Pharmacol Exp Ther. 1986 Aug;238(2):587-93.
Pharmacological comparison of ORF 17910, a potent, long-acting histamine H2-receptor antagonist, to cimetidine and ranitidine.

Katz LB, Scott CK, Shriver DA.

This paper describes the pharmacology of ORF 17910, a specific, long-acting histamine H2-receptor antagonist. ORF 17910 (ED50 = 0.26 mg/kg) is 26 and 2.7 times more potent p.o. than cimetidine and ranitidine, respectively, at inhibiting acid output in betazole-stimulated total gastric fistula dogs. When given i.v., ORF 17910 (ED50 = 0.06 mg/kg) is 3.6 times more potent than ranitidine. Qualitatively similar antisecretory potency differences are seen in rats (ED50 = 3.7 mg/kg intraduodenal). ORF 17910 retains 43 and 37% of its antisecretory potency 16 hr after dosing in dogs and rats, respectively, suggesting a long duration of action, whereas ranitidine is either inactive (rats) or loses 97% of its potency (dogs) at this time. When the parenteral and enteral (p.o. or intraduodenal) potencies of ORF 17910 and ranitidine are compared, ORF 17910 appears less bioavailable than ranitidine, although this difference is greater in the rat than in the dog and diminishes with time. In rabbit isolated parietal cell (pA2 = 7.96) and guinea pig isolated atria preparations (pA2 = 7.51), ORF 17910 is more potent than both cimetidine and ranitidine at inhibiting the effects of histamine. At high concentrations, the inhibitory effect of ORF 17910 in atria can not be overcome completely, a property which may contribute to its long duration of action in vivo. In several additional test systems, ORF 17910 does not exhibit any biologically significant pharmacology and appears to be specific for the histamine H2-receptor.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2874214&dopt=Abstract ranitidine






Acta Diabetol Lat. 1986 Apr-Jun;23(2):165-70.
The role of ranitidine infusion on glucose, insulin and C-peptide serum levels induced by oral glucose tolerance test in healthy subjects.

Gentile S, Marmo R, Costume A, Orlando C, D'Alessandro R, De Bellis G, Porcellini M, Coltorti M.

In 9 healthy subjects we evaluated the effect of a constant ranitidine infusion (100 mg) on glucose (mg/dl), insulin (microU/ml) and C-peptide (ng/ml) serum levels promoted by oral glucose tolerance test (75 g). Ranitidine significantly increased the area under concentration/time curves for glucose and insulin but not that of C-peptide. Our data indicate that ranitidine does not affect pancreatic insulin release nor peripheral glucose utilization and are consistent with the hypothesis that ranitidine influences the hepatic clearance of glucose and insulin both of which undergo high first-pass liver extraction.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3529778&dopt=Abstract ranitidine






Int J Clin Pharmacol Ther Toxicol. 1987 Mar;25(3):139-42.
Ranitidine disposition in severe hepatic cirrhosis.

Gonzalez-Martin G, Paulos C, Veloso B, Chesta J, Novoa X, Arancibia A.

The effect of severe liver disease on ranitidine disposition was evaluated by comparing its kinetics in 5 healthy subjects and 11 patients with alcoholic cirrhosis. Cirrhotic patients had severe liver disease as evidenced by the presence of ascites, hepatic encephalopathy, jaundice, muscle wasting, and low serum albumin, but creatinine clearance did not differ significantly between controls and cirrhosis. Following intravenous administration of ranitidine, systemic clearance was decreased in cirrhosis. These decrease may be associated with changes in renal function, and decrease in hepatic metabolism, usually present in patients with severe hepatic failure. The distribution volume of ranitidine was also decreased in cirrhotics, but the difference between patients and controls was not significant. Biological half-life was significantly longer in cirrhotic patients than volunteers. This difference may be due to decrease in total body clearance found in cirrhotic patients. It is concluded that patients with severe liver cirrhosis could have elevated plasma level of ranitidine and that a reduction of ranitidine dosage is warranted in these patients.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3557740&dopt=Abstract ranitidine