Chronobiol Int. 1991;8(4):267-76.
Intragastric pH and pharmacokinetics of intravenous ranitidine during sinusoidal and constant-rate infusions.

Sanders SW, Bishop AL, Moore JG.

Drug Research Center, University of Utah Medical Center, Salt Lake City 84132.

Six patients with healed duodenal ulcer completed two treatment periods with continuous i.v. infusion ranitidine. A 25-mg i.v. bolus was followed by a constant infusion at 6.25 mg/h or a sinusoidal infusion with infusion rates ranging from 3.125 to 9.375 mg/h. The sinusoidal infusion rate was designed to match the previously observed circadian changes in basal acid secretion. The peak infusion rate occurred at 19:30 h. A pharmacokinetic method was designed to predict the resultant plasma concentrations of ranitidine. Intragastric pH and plasma ranitidine concentration data were fit to a cosine function to evaluate circadian and ultradian rhythms. Plasma concentrations during the sinusoidal infusion exhibited a circadian rhythm according to model predictions. Cosinor analyses of the mean ranitidine plasma concentration data showed a mesor concentration of 237 ng/mL and amplitude of 76 ng/mL (coefficient of determination [CD] = 0.98). The acrophase in plasma concentration occurred at 2223 h, a delay of approximately 2.9 hours from the peak in the infusion rate. The constant-rate infusion resulted in a mean plasma concentration of 222 +/- 32 ng/mL. The 24-h mean intragastric pH values for the sinusoidal and constant regimens were 5.4 and 5.1, respectively (p = 0.170). The intragastric pH during the constant-rate infusion exhibited a significant circadian rhythm (CD = 0.52). The minimum pH (bathy-phase) occurred at 2031 h. No circadian rhythm was present during the sinusoidal-rate infusion (CD = 0.08). At the approximate time of the peak basal acid secretion, between 21:00 hours and midnight, the mean pH for the sinusoidal infusion was 5.77 versus 4.5 for the constant-rate infusion (p = 0.112). Sinusoidal infusions or alternate methods o




Hepatogastroenterology. 1989 Dec;36(6):490-3.
The effect of an oral morning dose of nizatidine and ranitidine on gastric acid secretion in duodenal ulcer patients.

Lazzaroni M, Porro GB.

Gastrointestinal Unit, L. Sacco Hospital, Milano, Italy.

The aim of this study was to compare the inhibitory effect and duration of action of a new H2-antagonist, nizatidine (150 mg per os), with ranitidine (150 mg per os) in a group of 10 patients with healed duodenal ulcer. The total inhibitory effect on acid output observed under basal conditions (30 min), during pentagastrin stimulation (120 min) and after stimulation (60 min), is overlapping. However, nizatidine showed a more rapid inhibitory activity -80%, and 31% higher than ranitidine with regard to basal acid output and maximum acid output, during the first hour of stimulation. On the other hand, ranitidine has a more prolonged antisecretory action--more than 27% and 54%, respectively, with regard to maximum acid output during the second hour and the period after hormonal stimulation. Also, variations in pepsin and acid output resulted in overlapping. In conclusion, these results, explainable by the pharmacodynamic property of the two drugs, confirmed the excellent inhibitory capacity of nizatidine, and furnish another reason for its use in clinical practice.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2575571&dopt=Abstract ranitidine






Aliment Pharmacol Ther. 1989 Jun;3(3):299-313.
Effect of BMY-25368, a potent and long-acting histamine H2-receptor antagonist, on gastric secretion and aspirin-induced gastric lesions in the dog.

Cavanagh RL, Buyniski JP.

Department of Pharmacology, Bristol-Myers Company, Syracuse, New York.

BMY-25368, 1-amino-2-[3-(3-piperidinomethylphenoxy) propylamino]-1-cyclobutene-3,4-dione, a new histamine H2-receptor antagonist, has been compared to ranitidine as an inhibitor of gastric acid secretion in the Heidenhain pouch dog. Intravenous infusion of BMY-25368 antagonized histamine-stimulated gastric secretion in a competitive manner. BMY-25368 also antagonized gastric secretion stimulated by pentagastrin, bethanechol and food. When compared to ranitidine in histamine-stimulated dogs, BMY-25368 was nine times more potent after bolus intravenous administration. Oral potency relative to ranitidine and ranged from 2.8 to 4.4, depending on the secretagogue used. BMY-25368 also exhibited a significantly longer duration of action than ranitidine. Thus, its potency relative to ranitidine after oral administration, in histamine-stimulated dogs, increased from 3.2 to 28 when determined 1-3 and 10-12 h post dose, respectively. BMY-25368 administered orally also antagonized aspirin-induced gastric lesions in the dog and was nine times more potent than ranitidine in this respect.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2577694&dopt=Abstract ranitidine






Braz J Med Biol Res. 1991;24(6):567-72.
Use of ampicillin plus ranitidine for Helicobacter pylori gastritis.

Ferrari AP, Geocze S, Lanzoni VP, Toledo MR, Trabulsi LR, Vilela MP.

Departamento de Gastroenterologia Clinica, Escola Paulista de Medicina, Sao Paulo, Brasil.

1. Helicobacter pylori (formerly Campylobacter pylori) is now recognized as an etiological factor in gastritis and duodenal ulcers and probably also gastric ulcers. Eradication of the bacteria is fundamental to avoid ulcer relapse. Although bismuth salts have been shown to be effective for treatment, they are not commercially available in Brazil. 2. We report an attempt to treat patients with Helicobacter pylori-associated gastritis with ampicillin (1000 mg twice daily for one month) and compare the results with the conventional treatment used in Brazil (ranitidine, 300 mg daily for one month) and with a combination of the two drugs. We studied 44 patients with histologically confirmed gastritis and with Helicobacter pylori, who were examined at the beginning and after one month of treatment. 3. Ampicillin associated with ranitidine was better than ampicillin or ranitidine alone for the treatment of gastritis. Although ampicillin may be more efficient in patients with lower acid output we did not find a statistically significant difference between these two groups (ampicillin vs drug combination), perhaps owing to the small number of patients studied. When ampicillin was combined with ranitidine there was 25% normalization of the histological picture of the gastric mucosa. 4. We conclude that ampicillin in combination with ranitidine may be a useful treatment for Helicobacter pylori-associated gastritis.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1823272&dopt=Abstract ranitidine






Gut. 1989 Oct;30(10):1313-22.
Effect of cimetidine and ranitidine on drug induced damage to gastric epithelial cell monolayers in vitro.

Romano M, Razandi M, Ivey KJ.

Department of Medicine, Long Beach VA Medical Center, California.

The effect of the H2 blockers cimetidine and ranitidine on drug induced damage to gastric cell monolayers has been evaluated in conditions independent of systemic factors and their anti-acid properties. Monolayers of mucous cells from a human cell line MKN 28, obtained from a human gastric adenocarcinoma, have been studied. Cell damage has been assessed qualitatively by trypan blue dye exclusion test and quantitatively by 51Cr release assay. Cimetidine and ranitidine significantly protected cultured cells against damage induced by sodium taurocholate decreasing taurocholate induced 51Cr release by 36% (p less than 0.001) and 28% (p less than 0.01), respectively. Cimetidine was also protective in concentrations lower than ranitidine. This protection was not prevented by the prostaglandin synthesis inhibitor indomethacin nor by the sulph-hydryl blocker N-ethylmaleimide. Incubation with cimetidine and ranitidine did not increase the production of PGE2 by cultured cells nor did it affect the cellular level of sulph-hydryl compounds. Cimetidine and ranitidine did not afford protection against damage induced by indomethacin and ethanol. Cimetidine in a concentration of 10 4M increased ethanol induced damage significantly. In conclusion (1) cimetidine and ranitidine protect gastric cells against taurocholate induced damage in vitro, independently of their anti-acid effect; (2) this protection is not mediated by prostaglandin E2 or sulph-hydryl compounds; (3) cimetidine and ranitidine do not protect gastric cells against damage induced by indomethacin and ethanol.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2583559&dopt=Abstract ranitidine






J Pharm Sci. 1989 Dec;78(12):990-4.
Inter- and intrasubject variations of ranitidine pharmacokinetics after oral administration to normal male subjects.

Shim CK, Hong JS.

College of Pharmacy, Seoul National University, Korea.

Inter- and intrasubject variations of ranitidine pharmacokinetics were examined following oral administration of ranitidine tablets (150 mg as base) under controlled conditions at a timed interval of one week (periods I and II) to 12 healthy male subjects. Significant secondary peaks in the plasma concentration-time curves were observed in all subjects in both periods. The first peak occurred at 0.5 to 2.5 h and the second peak at 3 to 6 h after the dosing. There were great variations in the plasma concentration-time profiles among subjects; for example, the area under the plasma concentration-time curve from time 0 to 12 h (AUC0-12) varied from 1905 to 5672 micrograms.h/mL. But bioavailability parameters of period I, such as maximum concentration of the first and second plasma peak (Cmax 1 and Cmax 2, respectively), time to first peak (tmax 1), AUC0-12, and AUC from time zero to infinity (AUC0-infinity), were correlated significantly with those of period II. These results suggest that the intrasubject variation of ranitidine pharmacokinetics is usually small over at least one week under the controlled conditions of this study, in spite of its great intersubject variation.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2614701&dopt=Abstract ranitidine






Pol Tyg Lek. 1989 Jul 3;44(27):639-41.
[Effect of cimetidine and ranitidine on bronchial reactivity in patients with asthma]

[Article in Polish]

Hofman J, Rutkowski R, Michalska I, Niklinska B, Chyrek-Borowska S.

The results of studies on the effect of cimetidine and ranitidine on the bronchial reactivity in a group of 10 patients with atopic bronchial asthma are discussed. The patients received 800 mg of cimetidine daily for 6 days and, after a three-day interval, 300 mg of ranitidine daily for a further 6 days. Bronchial reactivity was determined with the histamine test, according to Spector and Farr, before the administration of each drug and on the third and sixth days of each course of the treatment. A comparison of the effect of cimetidine and ranitidine on the bronchial reactivity in the same patients revealed that a 3-day exposure to each of the two drugs, cimetidine enhanced bronchial reactivity to a greater extent than ranitidine; the difference between the action of the two drugs being statistically significant (p less than 0.05). Bronchial reactivity was found to increase significantly after a 6-day treatment with each of the drugs but no statistically significant differences were noted comparing the effect of these drugs.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2637435&dopt=Abstract ranitidine






Mutat Res. 1989 Sep;227(1):13-6.
Genotoxicity of nitrosated ranitidine.

Franekic J, Skupnjak S, Matijasevic Z.

Faculty of Food Technology and Biotechnology, Zagreb, Yugoslavia.

The genotoxicity of ranitidine, widely used in the therapy of peptic ulcers, and of nitrosated ranitidine was examined in test systems with the bacteria Salmonella typhimurium for gene mutations, and with the yeast Saccharomyces cerevisiae D7 for reverse mutations and gene conversion. Under the experimental conditions applied, ranitidine was negative in both systems, while the product obtained by nitrosation in vitro was mutagenic for Salmonella strains TA100 and TA98 with and without metabolic activation. The largest increase of his+ revertants, 3 times greater than the control, was obtained in strain TA100 in the absence of S9 fraction. Nitrosated ranitidine was also recombinogenic for the yeast S. cerevisiae.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2671717&dopt=Abstract ranitidine






Agents Actions. 1989 Apr;27(1-2):202-4.
Comparison of the effects of cimetidine and ranitidine in histamine provocation tests in atopic asthma.

Hofman J, Rutkowski R, Michalska I.

Department of Allergology, Medical School in Bialystok, Poland.

The effects of cimetidine and ranitidine on the bronchial reactivity in the group of 10 patients with atopic bronchial asthma are presented. The patients received 800 mg of cimetidine daily for 6 days and, after a three-day interval, 300 mg of ranitidine daily for a further 6 days. Bronchial reactivity to histamine was determined before the administration of each drug and on the third and sixth days of each course of treatment. A comparison of the effect of cimetidine and ranitidine on the bronchial reactivity of the same patients revealed that after 3 days' exposure to each of the two drugs, cimetidine enhanced bronchial reactivity to a statistically (p less than 0.05) greater extent than ranitidine. Bronchial reactivity was found to increase significantly after 6 days of treatment with each of the drugs but no statistically significant differences were noted on comparing the effect of these drugs. The results seem to indicate that H2 receptor antagonists may cause bronchoconstriction in some patients with bronchial asthma. The blocking effect depends on the type of the drug used and is connected with the chemical structure of the compounds.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2750593&dopt=Abstract ranitidine