Wien Klin Wochenschr. 1983 Apr 29;95(9):310-2.
[Side effects and safety of the new histamine H2 receptor antagonist ranitidine in the long-term treatment of patients with stomach and duodenal ulcers]

[Article in German]

Meryn S, Potzi R, Brunner H, Pesendorfer FX, Pamperl H.

The safety and various side effects of ranitidine (2 X 150 mg daily), a new selective H2-receptor antagonist, were evaluated in the long-term treatment of patients with prepyloric or duodenal ulcer. A total of 6 adverse effects was reported by 5 out of 32 patients (18.7%). Thus, the overall incidence was low and almost half of the adverse effects involved minor or functional gastrointestinal symptoms. In no case were side effects severe enough to necessitate interruption of therapy. There were no detectable changes in haematological or biochemical blood parameters attributable to ranitidine. Long-term therapy with ranitidine appears to be safe and well tolerated; however, continued surveillance must be maintained.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6137111&dopt=Abstract ranitidine






Br J Clin Pharmacol. 1983 Aug;16(2):117-20.
The effect of ranitidine on the plasma clearance and hepatic extraction of indocyanine green in patients with chronic liver disease.

Dunk AA, Jenkins WJ, Burroughs AK, Walt RP, Osuafor TO, Sherlock S, Mackie S, Dick R.

Since hepatic clearance of ICG is reduced by H2-receptor antagonists in normal subjects, it has been suggested that they reduce liver blood flow. We have studied the effect of intravenous ranitidine on ICG clearance in twelve patients with chronic liver disease. Wedged and free hepatic venous pressure were measured before and after intravenous ranitidine in nine of the patients, and the hepatic extraction of ICG was determined in six patients. ICG clearance fell by 22 +/- 11% (s.e. mean) 60 min after ranitidine. In patients in whom ICG clearance fell after intravenous ranitidine the hepatic extraction of ICG was also reduced. There was no significant change in the gradient between wedged and free hepatic venous pressure after ranitidine. It is therefore unlikely that ranitidine lowers liver blood flow.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6137230&dopt=Abstract ranitidine






Drug Metab Dispos. 1984 Jan-Feb;12(1):106-10.
Effects of cimetidine and ranitidine on halothane metabolism and hepatotoxicity in an animal model.

Plummer JL, Wanwimolruk S, Jenner MA, Hall PD, Cousins MJ.

This study was undertaken to determine the effects of two H2-receptor antagonists, cimetidine and ranitidine, on halothane metabolism and hepatotoxicity in the hypoxic Fisher 344 rat model for halothane hepatitis. In this model, liver injury is caused by toxic intermediates formed during metabolism of halothane by a reductive pathway. Administration of cimetidine (120 mg/kg ip) 20 min prior to anesthesia led to inhibition of the reductive pathway, as assessed by measurement of the exhaled metabolites, 2-chloro-1,1,1-trifluoroethane and 2-chloro-1,1-difluoroethylene, during anesthesia, and urinary fluoride excretion in the 22-hr postanesthesia period. Oxidative metabolism of halothane, assessed by serum bromide concentrations 22 hr postanesthesia, was unaffected. Cimetidine administration provided partial protection against the hepatotoxic effect of halothane, as indicated by serum alanine aminotransferase activities 22 hr postanesthesia. When ranitidine HCl (120 mg/kg ip) was administered prior to anesthesia, reductive metabolism of halothane was unaffected, but the oxidative pathway was slightly inhibited. Ranitidine did not provide protection against halothane-induced liver injury. These results provide additional evidence that halothane hepatotoxicity in the hypoxic rat model is due to toxic intermediates formed during the reductive metabolism of halothane.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6141900&dopt=Abstract ranitidine






Clin Exp Pharmacol Physiol. 1984 Jan-Feb;11(1):61-9.
Effects of histamine and histamine antagonists on hepatic bile flow in the conscious sheep.

Lee SP.

The effects of histamine and histamine antagonists on bile flow have been studied using the cholecystectomized conscious sheep. Histamine stimulated bile flow in a dose-dependent manner (D50 = 15.7 micrograms/h per kg). Free water and HCO3-output were increased after intravenous histamine infusion. With histamine at 120 mg/h per kg, there was a 41.0 (s.d. = 4.6)% and 38.7 (s.d. = 4.2)% (n = 6) increase in bile volume and HCO3-output respectively. Bile salt concentration was decreased after intravenous histamine, but net bile salt secretory rate remained unchanged. There was no change observed in the molar ratios of bile salts: phospholipids: cholesterol. Total lipids were decreased from 2.2 (s.d. = 0.3) to 1.60 (s.d. = 0.4) g/dl (n = 6). The corrected lithogenic index did not change significantly. 14C-Erythritol clearance also increased during histamine infusion in a dose-dependent manner but did not correspond to increments in bile flow. The histamine H1-receptor antagonist, diphenhydramine 0.05-1.0 mg/h per kg did not alter histamine stimulated bile flow. The H2-receptor antagonists, cimetidine (0.5-4 mg/h per kg) and ranitidine (0.05-0.5 mg/h per kg) progressively reversed the histamine-induced choleresis. Maximum inhibitory effect was attained at 2.0 and 0.25 mg/h per kg for cimetidine and ranitidine, respectively. At these levels, variation of intravenous infusion of histamine did not result in competitive displacement of the inhibitory response by either cimetidine or ranitidine. Moreover, concomitant infusion of diphenhydramine at 1.0 mg/h per kg potentiated the inhibitory effect of cimetidine or ranitidine on histamine-induced choleresis. Histamine increases the bile salt independent component of hepatic bile flow.(ABSTRACT TRUNCATED AT 250 WORDS)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6143632&dopt=Abstract ranitidine






Int J Tissue React. 1984;6(2):181-4.
Comparative study with oxmetidine and ranitidine on acid secretion and gastrin release in the dog.

Soldani G, Del Tacca M, Polloni A, Bernardini C, Martinotti E.

The antisecretory potency of oxmetidine was compared with that of ranitidine for its action against gastric acid secretion induced by histamine and by 2-deoxy-D-glucose (2DG) in the conscious gastric-fistula dog. Oxmetidine, administered i.v. during histamine stimulation, was nearly as effective as ranitidine, with a similar duration of action, but it was about twice as potent as ranitidine against 2DG-stimulated acid secretion. In experiments with bombesin, both oxmetidine and ranitidine significantly decreased gastric acid secretion to a similar extent, without affecting plasma gastrin levels.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6145677&dopt=Abstract ranitidine






Int J Immunopharmacol. 1984;6(5):467-73.
Reversal of histamine-mediated immunosuppression by structurally diverse histamine type II (H2) receptor antagonists.

Badger AM, Young J, Poste G.

The effect of a series of structurally-diverse histamine type II (H2)-receptor antagonists on histamine-mediated immunosuppression of human peripheral blood lymphocytes (HPBL) has been examined. This analysis of structure--activity relationships was undertaken to examine the validity of the recent proposal arising from clinical studies that H2-receptor antagonists containing a furan ring were devoid of the effects on lymphocyte function reported previously in studies using cimetidine and other H2-receptor antagonists containing an imidazole nucleus. Cimetidine and two furan-containing antagonists, ranitidine and SKF 93479, were found to be devoid of any effect on PHA-induced proliferation of human peripheral blood lymphocytes over a wide concentration range (10(-4) to 10(-10)M). At high drug concentrations (10(-3)M) significant suppression of mitogen stimulation was observed but this was accompanied by significant cytotoxicity. All three antagonists were effective in reversing the suppression of PHA-stimulation of HPBL induced by exogenous histamine. Reversal of histamine-induced immunosuppression was obtained at drug concentrations (2.0 X 10(-4) to 1.0 X 10(-6)M) which were non-toxic and did not affect PHA-induced proliferation in the absence of histamine. Ranitidine was the most potent antagonist in reversing histamine-mediated immunosuppression. The ability of structurally-diverse H2-receptor antagonists to modify the action of histamine on lymphocyte function lends support to the view that histamine exerts its effects via classical H2-receptors. The ability of ranitidine to alter lymphocyte responsiveness in analogous fashion to cimetidine indicates that the possibility of alterations in immune function should be considered in clinical studies using ranitidine and other furan-containing H2-receptor antagonists




Farmaco [Sci]. 1983 Feb;38(2):135-42.
[Protective effect of ranitidine in acute experimental pancreatitis in the rat]

[Article in Italian]

Scarpignato C, Bertaccini G, Sarli L, Lupi M, Gafa M.

Acute experimental pancreatitis was induced in rats, with a polyethylene splint placed into the duodenum, by the closed duodenal loop technique. Ranitidine (20 mg . kg-1) or saline were administered intraperitoneally every 8 hrs, beginning 15 min prior to surgery. The degree of pancreatitis and the amylase to creatinine clearance ratio (ACCR) were evaluated in all the animals after sacrifice. Ranitidine-treated animals showed significant by reduced pancreatic damage and ACCR values in comparison with non-treated rats. These data confirm the efficacy of ranitidine as a preventive agent in the development of acute pancreatitis and suggest that controlled trials should be performed with this H2-antagonist in the human subyects with this disease.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6188631&dopt=Abstract ranitidine






J Pharm Sci. 1980 Oct;69(10):1155-7.
High-pressure liquid chromatographic determination of ranitidine, a new H2-receptor antagonist, in plasma and urine.

Mihaly GW, Drummer OH, Marshall A, Smallwood RA, Louis WJ.

An assay is described for the determination of a new H2-receptor antagonist, ranitidine, and its desmethyl metabolite in human plasma and urine. Alkalinized plasma or urine was extracted with methylene chloride, the organic phase was evaporated, and the reconstituted residue was analyzed by high-pressure liquid chromatography using a reversed-phase column. Two other identified metabolites of ranitidine, the S-oxide and N-oxide, were separated chromtographically from both ranitidine and the desmethyl metabolite. However, these metabolites could not be quantitative due to poor analytical recovery and interference from endogenous components. The sensitivity limits were 5 ng/ml for ranitidine and 15 ng/ml for desmethylranitidine. Plasma samples from two volunteers who were given oral ranitidine (0.1, 0.2, and 0.4 mg/kg) at 1-week intervals were assayed. Peak levels of 30--130 ng/ml were achieved between 40 and 120 min after dosage, followed by an elimination half-life of 2.9-3.9 hr. Plasma levels of ranitidine were still detectable at 8 hr but were below the sensitivity of the assay by 24 hr. Plasma levels of the desmethyl metabolite were seldom above the threshold sensitivity of the assay. Urinary excretion of unmetabolized ranitidine accounted for 77% of the administered dose, whereas only 4% appeared as desmethylranitidine.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6252316&dopt=Abstract ranitidine






Res Exp Med (Berl). 1981;178(2):151-4.
The new histamine H2-receptor antagonist ranitidine. Duration of action.

Dammann HG, Muller P, Kather H, Simon B.

The antisecretory effects of a new histamine H2-receptor antagonist, ranitidine hydrochloride, have been investigated on basal and pentagastrin-stimulated acid secretion in healthy volunteers 5 and 10 h after oral administration of 150 mg. In addition, the 24-h intragastric pH-profiles have been measured in patients undergoing parenteral nutrition after three doses of 150 mg ranitidine per day. A 40% inhibition of basal acid output has been noted even 10 h after drug intake. The intragastric pH-values were raised above 5 for at least 24 h. The new H2-antagonist ranitidine has been proven to be a potent and long-acting antisecretory compound.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6262889&dopt=Abstract ranitidine