HCO3- secretion in rat duodenum after treatment with omeprazole and ranitidine

The bicarbonate secretion by the duodenal mucosa, which is stimulated by luminal acid, is very probably important in mucosal protection against the acid. It was of interest to investigate whether long-term deprivation of the mucosa of this acid stimulus affected the alkali secretion. Sprague-Dawley rats were treated for 4-6 weeks with either omeprazole, 14 mg/kg body weight twice daily, or ranitidine, 300 mg/kg twice daily, by means of gastric intubation. The rate of bicarbonate secretion by the duodenal mucosa was determined in situ by continuous titration. Neither the basal secretion nor the increase in secretion in response to stimulation by prostaglandin E2 or luminal acid (pH 2.0 for 5 or 60 min) differed in treated animals from that in controls that had received placebo (p greater than 0.05). Thus, 4-6 weeks of treatment with omeprazole or ranitidine did not reduce duodenal mucosal bicarbonate secretion in the rat, nor did these drugs diminish the ability of this mucosa to respond to prolonged luminal acidification or luminally administered prostaglandin E2.     

24-hour intragastric acidity and plasma gastrin during long-term treatment with omeprazole or ranitidine in patients with reflux esophagitis

The reduction in intragastric acidity and the subsequent increase in plasma gastrin were compared during long-term treatment with either omeprazole or ranitidine in 19 patients with erosive reflux esophagitis. The patients received 40 mg omeprazole in the morning or 300 mg ranitidine twice daily. After healing, half the dose was given as maintenance treatment for 1 year. Intragastric acidity and plasma gastrin were measured 24 h before entry and monthly with the high dose and after 1, 6, and 12 months with the low dose. Omeprazole reduced intragastric acidity more effectively than ranitidine (p less than 0.001). This difference in efficacy was more pronounced during the daytime. Plasma gastrin increased more after omeprazole than after ranitidine (p less than 0.01), and both drugs showed a normal postprandial response and approached fasting levels before the next dose. During long-term treatment with 20 mg omeprazole in the morning no progressive alterations were observed in 24-h intragastric acidity or plasma gastrin.     

Nocturnal intragastric acidity during and after a period of dosing with either ranitidine or omeprazole

The magnitude and duration of changes in nocturnal intragastric acidity caused by 25 days of dosing with the antisecretory drugs ranitidine and omeprazole were investigated in a double-blind study of 22 healthy subjects. Nocturnal intragastric acidity was studied before (twice), during (on day 25), and after (every 3 days for 21 days) dosing with either 300 mg ranitidine at night or 40 mg omeprazole every morning. Three and six days after withdrawal of dosing with ranitidine, median integrated nocturnal intragastric acidity was increased significantly (17% and 14%, P = 0.01 and P = 0.05, respectively) compared with before dosing. Three days after withdrawal of dosing with omeprazole, median integrated nocturnal intragastric acidity was decreased significantly (-23%, P = 0.003). Compared with before dosing, no significant differences were seen in the ranitidine group between days 9 and 21 or the omeprazole group between days 6 and 21 after cessation of dosing. Fasting plasma gastrin concentration was measured on the morning of each study; compared with before treatment, the only significant elevations occurred on the last day of dosing with omeprazole (before, 4 pmol/L; during, 7 pmol/L). It is concluded that rebound intragastric hyperacidity after dosing with 300 mg ranitidine at night or sustained hypoacidity after dosing with 40 mg omeprazole every morning reflect transient disturbances of gastric function that are unlikely to be of clinical importance.     

Effects of omeprazole and pirenzepine on enterochromaffin-like cells and parietal cells in rat stomach

Purpose. The purpose of this study was to investigate the mechanism of the regulation of histamine synthesis in enterochromaffin-like cells, chemically and structurally, by treatment with omeprazole and pirenzepine. Methods. The ultrastructures of enterochromaffin-like cells and parietal cells were examined in rats treated with oral omeprazole (20 mg/kg) or intraperitoneal pirenzepine (1 mg/kg) administration. Serum gastrin concentrations, mRNA levels of H⁺-K⁺-ATPase and histidine decarboxylase, and the fundic concentrations of somatostatin and histamine were determined. Results. Pirenzepine treatment suppressed omeprazole-induced increases in serum gastrin levels and mRNA levels of H⁺-K⁺-ATPase and histidine decarboxylase. Pirenzepine also decreased omeprazole-induced increases of histamine concentration in fundic mucosa. Pirenzepine elevated somatostatin mRNA level, previously decreased by omeprazole treatment, in fundic mucosa. In the cytoplasm of enterochromaffin-like cells, omeprazole markedly reduced the numbers of vesicles and granules, but significantly increased their diameters, whereas pirenzepine treatment changed neither of these features. The densities and diameters of both vesicles and granules produced by treatment with omeprazole and pirenzepine were between those produced by treatment with omeprazole alone and pirenzepine alone. Conclusions. Omeprazole-induced hypergastrinemia and pirenzepine-induced somatostatin synthesis play important roles not only in histamine synthesis but also in ultrastructural changes in enterochromaffin-like cells. Received: September 13, 2000 / Accepted: January 12, 2001     

The effect of omeprazole or ranitidine treatment on 24-hour esophageal acidity in patients with reflux esophagitis

Twenty-two consecutive patients with gastroesophageal reflux and erosive or ulcerative esophagitis entered a double-blind, randomized study comparing the effect of 20 mg omeprazole once daily with that of 150 mg ranitidine twice daily on esophageal acidity. Ambulatory 24-h esophageal pH measurements were performed within 1 month before inclusion and after 3 weeks of medication. Omeprazole significantly (p less than 0.05) reduced the number of reflux (pH less than 4) episodes, the number of refluxes lasting greater than 5 min, and the total reflux time. In contrast, ranitidine significantly reduced only the total reflux time. When the two treatment groups were compared, a significant difference in favor of omeprazole was found for daytime and total reflux values, except for the longest reflux and the number of reflux episodes lasting greater than 5 min. Substantial differences, also in favor of omeprazole, were found with regard to the effect on endoscopic healing of the esophagitis.     

Gastric acid secretion and plasma gastrin during short-term treatment with omeprazole and ranitidine in duodenal ulcer patients.

The aim of this study was to evaluate changes in peptic acid secretion, and in fasting and meal-stimulated plasma gastrin levels after a 7-day course of omeprazole 30 mg/day or ranitidine 300 mg/day, administered in accordance with a randomized, double-blind, double-dummy protocol. Ten duodenal ulcer patients were studied. Their acid and pepsin output was determined prior to and after treatment. Plasma gastrin levels were also determined under basal conditions on day 7 of treatment, and 24 hours after the last administration of the drug. With regard to acid output, omeprazole resulted in a 98% reduction in BAO and an 80% reduction in PAO, both significantly greater than those achieved with ranitidine (BAO 50%, PAO 25%). No significant changes in pepsin secretion were observed. The increase in fasting plasma gastrin observed after ranitidine and omeprazole was 86% and 242%, respectively, on day 7, and 13% and 103% twenty-four hours after final dose. Increases in meal-stimulated plasma gastrin were, respectively, 126% and 125% on day 7 and 8 after omeprazole, whereas the increase with ranitidine was 62% only on day 7 of treatment, with subsequent normalization. In addition to confirming the well-known effect of omeprazole on the physiology of gastric secretion, our data show that administration of therapeutic doses of traditional H2-antagonists is accompanied by a secondary hypergastrinemia, which is rapidly reversible after discontinuation of therapy.     

Omeprazole, cimetidine, and ranitidine: inhibition of acid production in isolated human parietal cells

The antisecretory properties of omeprazole, cimetidine, and ranitidine were studied in vitro, using human gastric mucosal cells, which were obtained by sequential pronase and collagenase incubation of small tissue specimens obtained by endoscopic biopsy. Acid production was measured as the accumulation of radioactive aminopyrine in the acid compartments of the parietal cells. Acid production was stimulated via H2-receptors by histamine (10(-4) M or 5 X 10(-6) M) and via intracellular mechanisms by db-cAMP (10(-3) M). Omeprazole induced a dose-dependent inhibition of acid production for all stimulators (IC50 = 2 X 10(-7) M and 3 X 10(-8) M with high and low concentrations of histamine, respectively, and 5 X 10(-6) M with db-cAMP). The H2-receptor antagonists dose-dependently inhibited the histamine-stimulated acid production (IC50 for cimetidine = 10(-5) M and 10(-6) M and for ranitidine = 10(-5) M and 2 X 10(-7) M for high and low concentrations of histamine, respectively). Neither cimetidine nor ranitidine inhibited acid production after intracellular stimulation with db-cAMP. Omeprazole reduced the aminopyrine accumulation stimulated by histamine (10(-4) M) already within 5-10 min, whereas cimetidine (10(-3) M and ranitidine (10(-4) M) required 20-30 min. The unstimulated level of acid production was also inhibited by omeprazole but not by the H2-receptor antagonists.     

Comparison of three triple regimens with omeprazole or ranitidine bismuth citrate for Helicobacter pylori eradication

BACKGROUND: Regimens with ranitidine bismuth citrate (RBC) or omeprazole (O) are effective in eradicating Helicobacter pylori. This randomized, open, multicentre trial compares three different regimens with these drugs. METHODS: Consecutive H. pylori +ve outpatients were included. The alternative regimens were: 1) O 20 mg, clarithromycin (C) 250 mg and metronidazole (M) 500 mg (O.C.M), 2) RBC 400 mg, C 250 mg and M 500 mg (RBC.C.M), 3) RBC 400 mg, tetracycline (T) 1000 mg and M 500 mg [RBC.T.M]. All drugs were given twice daily for 7 days. H. pylori infection was assessed with H. pylori urea breath tests. RESULTS: 426 H. pylori +ve patients were included (mean age 58 years [range 18-88], male/female: 244/182). The eradication rates (intention to treat) in the O.C.M, RBC.C.M and RBC.T.M groups were 117/137 (85%), 141/146 (97%) and 117/143 (82%), respectively (P < 0.001, overall assessment). There were no significant differences in side effects between the alternatives. CONCLUSION: In this trial, RBC.C.M was the most effective one, it was well tolerated and compliance was satisfactory. RBC.T.M is an alternative to regimens with clarithromycin.     

Effects of ranitidine on regenerating parietal cells. A stereologic study

In this work, we have carried out a stereological and morphological study in order to verify the effects of Ranitidine on regenerating parietal cells. We have used a control group and operated or non-operated groups treated with 2, 10 and 50 mg/kg/day Ranitidine. In operated groups an ulcer was provoked by cauterization with a metallic plate in the gastric fundus. Groups treated with high doses of Ranitidine showed an increase in the connective tissue of the gastric mucosa. The stereological study in treated groups shows a decrease in the parietal volume density, and an increase in the cellular profile. Changes detected in the parietal volume density would originate a decrease in the production of CIH.     

The effects of rabeprazole on parietal cells and enterochromaffin-like cells in rats: a comparison with omeprazole

Background. We investigated the effects of rabe-prazole compared with those of omeprazole on enterochromaffin-like cells and parietal cells in rats. Methods. Rabeprazole or omeprazole was administered for 7 days by intraperitoneal injection (100 mg/kg or 20 mg/kg once a day) and the serum gastrin concentration, the antral density of G cells and D cells, fundic histamine content, fundic H⁺, K⁺-ATPase mRNA level, and parietal cell morphology were determined. Results. Both rabeprazole and omeprazole inhibited gastric acid secretion and increased the intragastric pH to over 6.5, as well as causing a marked increase in the serum gastrin concentration. The serum gastrin level was lower with rabeprazole treatment than with omeprazole treatment at both doses. Also, the antral G-cell density was higher with omeprazole than with rabeprazole, while the increase in both the histamine content and the H⁺, K⁺-ATPase mRNA level in the fundic mucosa was higher with omeprazole treatment at both doses, with the difference being significant at 100 mg/kg. Ultrastructural examination indicated that the stimulation of parietal cells by omeprazole was stronger than that by rabeprazole. Conclusions. Rabeprazole treatment does not drive enterochromaffin-like cells and parietal cells as strongly as omeprazole treatment despite its potent acid suppressive effect, suggesting that it represents a new generation of proton pump inhibitors. Received: March 16, 2001 / Accepted: August 10, 2001     

Healing and relapse of reflux esophagitis during treatment with ranitidine

In 108 patients the healing and relapse of reflux esophagitis, defined endoscopically by the presence of epithelial defects (erosions and ulcerations) of the esophageal mucosa, were studied. In the first study, with open treatment of ranitidine, the healing rate after 6 wk was 50%. The most important factor that negatively influenced healing was the extent of esophageal erosions. Patients with isolated erosions had a 6-wk healing rate of 78%; the healing rate was 38% in patients with longitudinally confluent lesions and 23% in those with circumferential erosions of the distal esophagus. Smoking also had an unfavorable effect. Age, sex, duration of history, body weight, and alcohol consumption were not related to outcome. Symptoms improved during treatment with ranitidine, but the correlation between symptoms and endoscopic findings at 6 wk was weak. In the second study, relapse was investigated in 61 patients with healed esophagitis in a randomized, double-blind trial comparing placebo and ranitidine (150 mg at bedtime for 6 mo). In both groups, relapse occurred in more than one-third of the patients, with no significant difference between ranitidine and placebo treatment. Patients with worse daytime symptoms at the time of previous healing had a higher relapse rate. The initial severity of esophagitis and smoking did not influence recurrence. Thus, the initial endoscopic findings are of prognostic value in reflux esophagitis. Smoking retards healing. Low-dose maintenance treatment with ranitidine does not prevent relapse.     

Mitogen stimulation of peripheral blood lymphocytes of duodenal ulcer patients during treatment with cimetidine or ranitidine

During a double-blind randomised clinical trial of cimetidine and ranitidine in the management of duodenal ulcer, the response of patients' peripheral blood lymphocytes to optimal mitogenic stimulation in vitro has been measured. Treatment with cimetidine, but not ranitidine, was associated with a significant increase in the proportion of peripheral blood lymphocytes responding to this optimal mitogenic stimulation. We conclude that these effects of cimetidine may not be mediated at classical histamine H2-receptors.     

Gastrin stimulates the self-replication rate of enterochromaffinlike cells in the rat stomach. Effects of omeprazole, ranitidine, and gastrin-17 in intact and antrectomized rats

The enterochromaffinlike cells in the rat stomach are rich in histamine and are thought to be under the influence of gastrin. The effect of sustained endogenous and exogenous hypergastrinemia on the activity and proliferation rate of the enterochromaffinlike cells was studied by determining the histidine decarboxylase activity and histamine concentration and by combining histamine immunocytochemistry and autoradiography after in vivo labeling with [3H]thymidine. The proliferation rate of the stem cells in the oxyntic mucosal progenitor zone was also studied. Exogenous hypergastrinemia was induced by infusion of rat gastrin-17 (60 nmol.kg-1.day-1). Endogenous hypergastrinemia was induced by inhibition of gastric acid secretion with omeprazole (80 mumol.kg-1.day-1) or ranitidine (1200 mumol.kg-1.day-1). The effect of omeprazole was also studied in antrectomized rats. In intact rats, all treatments resulted in elevated plasma gastrin levels and were accompanied by an increase in the histidine decarboxylase activity and the histamine content of the oxyntic mucosa. This resulted in an increase in the enterochromaffinlike cell proliferation rate, leading to enterochromaffinlike cell hyperplasia. The number of labeled stem cells was increased, but this effect was not as pronounced as in the enterochromaffinlike cells. In antrectomized rats, the inhibition of acid secretion by omeprazole did not result in elevated plasma gastrin or in an increase in the activity or number of enterochromaffinlike cells, indicating that omeprazole per se had no effect on these cells. These data support the view that gastrin stimulates the proliferation rate of both enterochromaffinlike cells and stem cells. Gastrin also stimulates the activity of the enterochromaffinlike cells.     

Double blind multicentre comparison of omeprazole 20 mg once daily versus ranitidine 150 mg twice daily in the treatment of cimetidine or ranitidine resistant duodenal ulcers.

The purpose of the present study was to compare omeprazole 20 mg once daily and ranitidine 150 mg twice daily in healing duodenal ulcers unhealed by previous treatment with cimetidine greater than or equal to 0.8 g or ranitidine greater than or equal to 0.3 g daily for at least six weeks. In a double blind multicentre trial, 151 patients were randomly assigned to either omeprazole or ranitidine. Clinical assessments and endoscopies were carried out at two and four weeks. Patients characteristics were similar in both groups. Statistical analysis (chi 2 test) did not show any significant difference in healing rate (p greater than 0.20) irrespective of the method of calculation. On an 'intent-to-treat' analysis (n = 151), healing was: omeprazole 46.6%, ranitidine 43.3% at day 15 and omeprazole 70.7%, ranitidine 68.4% at day 29; and among the patients who completed treatment, healing was: omeprazole 48.3%, ranitidine 46.3% at day 15 (n = 125; 95% confidence interval of the difference--17 to 21) and omeprazole 79.6%, ranitidine 75.4% at day 29 (n = 115; 95% confidence interval of the difference--13 to 21). After a further four weeks treatment with omeprazole, healing occurred in 16/20 (80%) who still had active disease at day 29. Patients on omeprazole and on ranitidine experienced similar decrease in day time and night time epigastric pain and in heartburn. Multivariate analysis (logistic regression) did not indicate any influence on age, sex, smoking and alcohol habits, previous drug administered, duodenitis and duodenal erosions on the healing rate. In this model, healing rate was not significantly influenced by previous treatment duration (p = 0.09 at day 15 and p greater than 0.2 at day 29) but was significantly influenced by ulcer size (p = 0.04 at day 15 and p = 0.02 at day 29). Forty one patients complained of adverse events: 19 on omeprazole (four trial withdrawals), 22 on ranitidine (three trial withdrawals).     

Comparison of omeprazole and ranitidine in treatment of refractory gastroesophageal reflux disease in patients with gastric acid hypersecretion

Secretion of gastric acid and volume, serum gastrin concentration, and ambulatory 24-hr esophageal pH monitoring were evaluated prospectively in 12 patients with idiopathic gastric acid hypersecretion (basal acid output greater than 10.0 meq/hr) undergoing treatment for refractory chronic long-standing pyrosis. Treatment lasted six months and consisted of three months of ranitidine (mean 2150 mg/day, range 1200–3000 mg/day), followed by three months of omeprazole (mean 33 mg/day, range 20–60 mg/day). Both ranitidine and omeprazole significantly reduced gastric acid output (P<0.001) and gastric volume output (P<0.001) compared to a basal evaluation and resulted in complete disappearance of pyrosis. Total reflux time (percent 24 hr intraesophageal pH less than 4) was significantly reduced by ranitidine (P<0.02) and omeprazole (P<0.001) compared to basal evaluation; however, the effects of omeprazole were significantly greater than ranitidine (P<0.05). Omeprazole caused a significant increase in serum gastrin concentration compared to both basal and ranitidine (P<0.05). Endoscopically documented erosive esophagitis was present in nine of the 12 patients, and seven of the 12 patients had Barrett's epithelium. All 12 patients had complete resolution of pyrosis and healed esophagitis by six months, but no significant endoscopic regression was observed in the extent of Barrett's epithelium. No side effects occurred with these high doses of ranitidine or omeprazole. These results indicate that high-dose ranitidine and omeprazole are effective therapy for refractory gastroesophageal reflux disease. However, with omeprazole, total reflux times are reduced more than with ranitidine, often into the normal range. That marked reduction of gastric acid secretion with omeprazole, which greatly reduces total reflux times, accounts for the significant elevation of serum gastrin concentration seen during omeprazole therapy.     

Effect of cimetidine, ranitidine, famotidine and omeprazole on hepatocyte proliferation in vitro

Recently reports have indicated that both cimetidine and ranitidine delay cell proliferation in rats following 70% partial hepatectomy and result in an increased mortality following this procedure. The present study was designed to determine whether three H2 blocking agents (cimetidine, ranitidine, famotidine) and a new, powerful antisecretory drug (omeprazole) specifically influence hepatocyte proliferation in primary culture. Hepatocytes were isolated from livers of normal male rats by the standard collagenase perfusion technique. Hepatic DNA synthesis and percent of labelled nuclei were determined after 48 h incubation. Hepatocytes in culture were incubated with the H2 blocking agents and omeprazole or with different concentrations of serum obtained from sham-operated or 70% hepatectomized rats treated or not with the same agents. Rats were injected intraperitoneally at 8:00 a.m. on two consecutive days. In hepatectomized rats, the first dose was injected at 8:00 a.m. immediately after surgery, the second, 24 h later. The serum of sham-operated or 70% hepatectomized rats that did not receive drugs served as control. No changes in DNA synthesis, percentage of labelled nuclei and transaminase were detected when the agents were added to the hepatocytes in culture at concentrations within the effective pharmacological dosage and 30 times higher. Similarly, no changes in these parameters were obtained when different concentrations of serum obtained from sham-operated rats treated with H2 blocking agents or omeprazole were added to the basal culture medium. However, a significant inhibition of DNA synthesis and of percentage of labelled nuclei was observed when hepatocytes were incubated in the presence of serum from 70% hepatectomized rats that had been treated with cimetidine or with ranitidine. The serum of 70% hepatectomized rats treated with famotidine and omeprazole had no effect on hepatocyte proliferation in vitro. No effect on transaminase was found in these conditions.     

A double-blind, randomized, parallel group study of omeprazole and ranitidine in Korean patients with gastric ulcer

Abstract The efficacy of the proton pump inhibitor omeprazole, 20 mg every morning, was compared with that of the H₂-receptor antagonist ranitidine, 150 mg every morning and at bedtime, in a double-blind randomized parallel group study in 250 patients with gastric or prepyloric uicers. At both 4 and 8 weeks, significantly more patients had healed ulcers in the omeprazole group than the ranitidine group, whether the results were analysed on a per-protocol or an intention-to-treat basis. At 4 weeks, 74% of patients in the omeprazole group were healed compared with 51% in the ranitidine group ( P = 0.001), and at 8 weeks the corresponding values were 99 and 82% ( P = 0.001, per-protocol cohort). Omeprazole treatment and small ulcer size significantly increased the probability of healing, but smoking had no significant effect. Patients in the omeprazole group had significantly fewer occurrences of daytime epigastric pain during the first 4 weeks than the ranitidine group ( P = 0.0037), as shown by their diary cards. Both treatments were well tolerated.     

Intragastric volatile N-nitrosamines, nitrite, pH, and Helicobacter pylori during long-term treatment with omeprazole

BACKGROUND & AIMS: This study evaluated the effect of long-term gastric acid suppressive therapy with omeprazole on intragastric levels of carcinogenic N-nitrosamines and related parameters. METHODS: Forty-five patients on long-term omeprazole medication (mean, 35 months) and 13 healthy subjects without medication participated. Volatile N-nitrosamines were determined in gastric juice and urine. Intragastric pH, nitrite, nitrate, and H. pylori status were determined. DNA isolated from gastric biopsy specimens was analyzed for precarcinogenic alkyl-DNA adducts. RESULTS: The intragastric pH in patients was significantly higher compared with controls (P = 0.0001). Gastric nitrite levels in patients were nonsignificantly higher. There was no difference in total levels of intragastric volatile N-nitrosamines between patients and controls, however, urinary N-nitrosodimethylamine excretion was higher in patients (P = 0.001). On omeprazole, Helicobacter pylori-positive vs. -negative patients had a nonsignificantly higher intragastric nitrite level and higher urinary N-nitrosodimethylamine excretion. No alkyl-DNA adducts could be detected in gastric epithelium. CONCLUSIONS: Increased intragastric pH caused by long-term treatment with omeprazole does not result in increased intragastric levels of nitrite and volatile N-nitrosamines. The significantly higher urinary N-nitrosamine excretion implies the risk of increased endogenous formation of N-nitrosamines during long-term omeprazole treatment. This risk may be higher in H. pylori-positive patients.