Am J Hosp Pharm. 1990 Jul;47(7):1580-4.
Stability of ranitidine hydrochloride at dilute concentration in intravenous infusion fluids at room temperature.

Galante LJ, Stewart JT, Warren FW, Johnson SM, Duncan R.

Department of Analytical Chemistry, Glaxo Inc., Research Triangle Park, NC.

The stability of ranitidine at low concentration (0.05 mg/mL) in five intravenous infusion solutions (0.9% sodium chloride, 5% dextrose, 10% dextrose, 5% dextrose with 0.45% sodium chloride, and 5% dextrose with lactated Ringer's injections) was studied. Admixtures were stored for seven days at room temperature in 150-mL and 1-L polyvinyl chloride infusion bags. Ranitidine stability in 0.9% sodium chloride injection and in 5% dextrose injection was also examined for up to 28 days, and these data were compared with data obtained at higher ranitidine concentrations (0.5-2.0 mg/mL). At intervals during the storage periods, color, clarity, and solution pH were examined and ranitidine content was determined by a stability-indicating high-performance liquid chromatographic assay. Ranitidine content remained greater than 90% of the initial concentration for more than 48 hours in all infusion fluids except 5% dextrose with lactated Ringer's injection. No visual changes or appreciable changes in pH were observed for any of the solutions. At the dilute concentration, ranitidine was markedly more stable after eight hours in 0.9% sodium chloride injection than in 5% dextrose injection. In 0.9% sodium chloride injection, ranitidine concentrations remained above 95% for up to 28 days, but drug concentrations in 5% dextrose injection fell below 90% after seven days. Stability in 5% dextrose injection improved as ranitidine concentrations increased from 0.05 to 2.0 mg/mL. Ranitidine (0.05 mg/mL) is stable for at least 48 hours at room temperature in all infusion fluids tested except 5% dextrose with lactated Ringer's injection.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2368751&dopt=Abstract ranitidine






Agents Actions. 1990 Apr;30(1-2):191-4.
Ranitidine but not famotidine releases acetylcholine from the guinea pig myenteric plexus.

Poli E, Coruzzi G, Bertaccini G.

Institute of Pharmacology, University of Parma, Ospedale Maggiore, Italy.

The effects of the histamine H2-receptor antagonists ranitidine and famotidine on acetylcholine release have been studied in the guinea pig myenteric plexus longitudinal muscle preparation incubated with [3H]-choline. Ranitidine (3 x 10(-5)-3 x 10(-4) M) dose-dependently increased the resting release of acetylcholine and that evoked by electrical stimulation. The effect was present only in strips perfused with 10(-5) M physostigmine. The effect of ranitidine was inhibited by tetrodotoxin and hexamethonium. Famotidine (10(-5)-3 x 10(-4) M) was totally ineffective in modifying both the resting release and that evoked by field stimulation. Ranitidine did not antagonize the inhibitory effect of oxotremorine, which specifically activates negative feedback mechanisms via presynaptic muscarinic receptors.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2371921&dopt=Abstract ranitidine






Dig Dis Sci. 1990 Sep;35(9):1140-5.
Plaunotol inhibits postprandial gastrin release by its unique secretin-releasing action in humans.

Shiratori K, Watanabe S, Takeuchi T, Shimizu K.

Department of Medicine and Gastroenterology, Tokyo Women's Medical College, Japan.

Plaunotol, an acrylic diterpene alcohol, is a new antiulcer agent derived from the "plau-noi" plant and has been reported to stimulate the release of endogenous secretin in humans. We investigated the effect of plaunotol on postprandial gastrin release, comparing it to the effect of exogenous secretin in a physiological dose in eight healthy volunteers. Four sets of experiments were performed in each volunteer: (1) meal alone, (2) meal after intravenous ranitidine (50 mg), (3) meal after oral administration of plaunotol (320 mg) in addition to ranitidine, and (4) meal after ranitidine with simultaneous intravenous infusion of secretin (0.03 CU/kg/hr). The postprandial increase in plasma secretin concentration was significantly reduced by ranitidine, while postprandial gastrin release was markedly exaggerated. Plaunotol in combination with ranitidine significantly increased secretin release and inhibited gastrin release after a meal. Intravenous infusion of secretin resulted in significant suppression of postprandial gastrin release exaggerated by ranitidine. The present study indicates that plaunotol inhibits postprandial gastrin release by its unique secretin-releasing action.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2390929&dopt=Abstract ranitidine






Digestion. 1990;45(4):181-8.
Effect of 20 weeks' ranitidine treatment on plasma gastrin levels and gastric enterochromaffin-like cell density in the rat.

Wallmark B, Skanberg I, Mattsson H, Andersson K, Sundler F, Hakanson R, Carlsson E.

Gastro-Intestinal Research, AB Hassle, Molndal, Sweden.

In this study, the effect of ranitidine treatment on the activation and proliferation of rat gastric enterochromaffin-like (ECL) cells was investigated. The drug was given in a high dose in the food (1.7-1.8 g/kg/day) for 20 weeks. This dose corresponds to the high dose given in the ranitidine oncogenicity study performed by Glaxo. With this dose regimen ranitidine induced hypergastrinaemia for 10 h of the day. The duration and the extent of the hypergastrinaemia closely followed the occurrence of ranitidine in plasma, strongly suggesting that the hypergastrinaemia was secondary to inhibition of acid secretion. Following 20 weeks treatment with ranitidine, both the relative weight of the stomach and that of the oxyntic mucosa were increased. The oxyntic histamine concentration and ECL-cell density were also increased significantly. These results show that when ranitidine is given in the diet the resulting hypergastrinaemia, which had a duration of 10 h each day, leads to a general increase in the oxyntic mucosal weight and a proliferation and activation of the ECL cells, indicating that sustained hypergastrinaemia is not a necessary requirement for development of ECL-cell hyperplasia.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2401392&dopt=Abstract ranitidine






Digestion. 1990;45(4):189-95.
Enterochromaffin-like cell carcinoids in the rat gastric mucosa following long-term administration of ranitidine.

Havu N, Mattsson H, Ekman L, Carlsson E.

Safety Assessment AB Astra, Sodertalje, Sweden.

Long-term administration of some long-acting inhibitors of gastric acid secretion has been associated with the development of gastric enterochromaffin-like (ECL)-cell carcinoids in the rat. It has been argued that short-acting, surmountable histamine H2-receptor blockers such as ranitidine do not cause carcinoids. In this study, female rats (n = 100) were treated for 2 years with the histamine H2-receptor blocker ranitidine, 2 g/kg/day in the diet. Specimens from the stomachs of all rats, including 50 controls, were stained for argyrophil cells. Plasma gastrin and ranitidine levels were measured in separate groups of rats at different times during the study. The mean plasma level of ranitidine was 37.5 mumol/l, measured at midnight when the maximal level after food intake was expected. The resulting acid inhibition was associated with an approximately 3-fold increase in plasma gastrin which persisted throughout the whole period of the study. The ranitidine treatment resulted in a pronounced hyperplasia of gastric ECL cells. In 19 rats carcinoids were found, 4 of which were micro-invasive. No carcinoids were found in the control animals. The results provide further support for the gastrin mechanism, i.e. that the development of ECL-cell carcinoids in the rat gastric mucosa is a consequence of prolonged hypergastrinaemia and is not a unique effect of any individual acid-inhibiting drug.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2401393&dopt=Abstract ranitidine






Aliment Pharmacol Ther. 1989 Oct;3(5):471-9.
The effects of fasting on 24-h gastric secretion of patients with duodenal ulcers resistant to ranitidine.

Johnston DA, Wormsley KG.

Ninewells Hospital, Dundee, Scotland.

We compared the effects of fasting and feeding on the antisecretory actions of ranitidine in 19 patients whose duodenal ulcers remained unhealed or relapsed despite treatment with the drug. Nine of the patients received, and continued with, 150 mg ranitidine b.d. and 10 took 300 mg ranitidine b.d. In all patients, gastric secretion was inhibited during the night, with near-neutral pH and acid output less than an average of 2 mmol in 8 h. Gastric secretion was not inhibited during the day by either of the therapeutic regimens. However, on the day when the patients fasted, gastric acidity was, on average, 20-50 mmol/L less than on the day when food was consumed. Food-induced interference with the therapeutic inhibition of gastric secretion produced by H2-receptor antagonists may be responsible for the unsatisfactory clinical response of some patients with duodenal ulcers. Prolonged fasting can improve the control of gastric secretion and may allow resistant ulcers to heal.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2518860&dopt=Abstract ranitidine






Plucne Bolesti. 1991 Jan-Jun;43(1-2):89-93.
[The effect of ranitidine on theophylline pharmacokinetics in patients with obstructive lung disease]

[Article in Croatian]

Paranos S, Despotovic N, Vidanovic M, Bojovic I, Milovanovic M, Dmitrovic V.

Klinicko-bolnicki centar "Zvezdara", Klinicki institut za alergologiju i klinicku imunologiju, Beograd.

The study was performed in 20 patients with mild and moderately severe forms of bronchial asthma or chronic obstructive bronchitis. Theophylline for oral use (sustained release form) and ranitidine was used in the first group of patients (7 females and 3 males, mean years of age 37.9). Dosage of theophylline from patients' sera was monitored prior and at 3, 6, and 12 hours beginning with the initial morning dose. The second group of patients (9 females and 1 male, mean age 46.3 years) were on ranitidine therapy along with 250 mg intravenous theophylline-ethylene-diamine. Fractionated dosage of theophylline was made within 12 hours. Pharmacokinetic parameters were calculated according to the concentration of theophylline in the sera of patients in the second group. In the sera of patients in the first group significantly higher concentrations of theophylline were found at 3 and 6 hour of the initial morning dose (p less than 0.05). In the second group a significant difference was not registered for the assessed pharmacokinetic parameters. This investigation indicates that there are individual differences of the metabolism of theophylline drugs with concommitant use of ranitidine.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1766997&dopt=Abstract ranitidine






Anaesthesia. 1989 Jul;44(7):590-1.
Sodium bicarbonate as a single dose antacid in obstetric anaesthesia.

Mathews HM, Moore J.

Department of Anaesthetics, Queen's University of Belfast.

Gastric pH and volumes were measured in 84 women who had general anaesthesia for emergency Caesarean section. Forty-eight received only 20 ml 8.4% sodium bicarbonate immediately before induction of anaesthesia and 36 ranitidine 150 mg 6-hourly during labour in combination with NaHCO3. Gastric pH was less than 2.5 in four women who received only bicarbonate. All aspirates from the ranitidine plus bicarbonate group had a pH greater than 2.5. Mean volumes of gastric content aspirated were 87 (SD 87.4) and 60 (SD 46.3) ml for the bicarbonate alone and bicarbonate plus ranitidine series respectively. These differences were not significant. Twenty millilitres of 8.4% NaHCO3 cannot be recommended as a single dose antacid for emergency Caesarean section. Ranitidine plus bicarbonate is considered a reliable antacid regimen to ensure elevation of gastric pH to safe levels.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2549802&dopt=Abstract ranitidine






Chronobiol Int. 1991;8(3):186-93.
Effect of basal gastric acid secretion on the pharmacodynamics of ranitidine.

Sanders SW, Ballersteros MA, Hogan DL, Koss MA, Isenberg JI.

Drug Research Center, University of Utah School of Medicine, Salt Lake City.

Twelve patients with inactive ulcer disease were administered placebo and ranitidine via bolus and continuous intravenous infusions, at doses ranging from 50 every 8 h, to 12.5 mg/h for 24 h. Gastric acid was collected for 20 min each h for 24 h, and ranitidine serum concentrations were measured approximately every 2 h, during each of the six study periods. Cosinor analysis of gastric acid secretion during placebo treatment revealed a significant circadian rhythm in all subjects. Mesor acid output ranged from 1.7 to 11.6 mmol/h (mean 5.6 +/- 2.8 mmol/h) and the amplitude ranged from 0.7 to 6.5 mmol/h (mean 2.8 +/- 1.6 mmol/h). Peak acid output (acrophase) occurred at 10 p.m. +/- 3 h. A pharmacodynamic model, relating ranitidine serum concentration to hourly acid secretion, was derived, which incorporated the circadian change in basal acid output. Data for this fractional response model included basal acid secretion--as determined by time of day, measured acid secretion, and associated serum ranitidine concentration. The 50% inhibitory concentration (IC50) for ranitidine ranged from 10-75 ng/ml, with a mean of 44 ng/ml. The variation in IC50 and in basal acid secretion combined to produce a wide variation in the pharmacodynamic response to ranitidine. The model-predicted serum concentrations, required to maintain acid secretion at 0.1 mmol/h, ranged from 250 to 1550 ng/ml, at the time of peak evening acid secretion. Despite a constant degree of acid inhibition by ranitidine during the day, higher serum concentrations are required during times of peak acid output to maintain adequate suppression of hydrogen ion secretion.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1794156&dopt=Abstract ranitidine