Omeprazole. A review of its use in Helicobacter pylori infection, gastro-oesophageal reflux disease and peptic ulcers induced by nonsteroidal anti-inflammatory drugs

Omeprazole is a well studied proton pump inhibitor that reduces gastric acid secretion. This review examines its use in Helicobacter pylori infection, gastro-oesophageal reflux disease (GORD) with or without oesophagitis and gastrointestinal damage caused by nonsteroidal anti-inflammatory drugs (NSAIDs). Optimal omeprazole regimens for anti-H. pylori therapy are those that administer the drug at a dosage of 40 mg/day (in 1 or 2 divided doses) for 7, 10 or 14 days in combination with 2 antibacterial agents. As a component of 3-drug regimens in direct comparative studies, omeprazole was at least as effective as lansoprazole, pantoprazole, bismuth compounds and ranitidine. However, a meta-analysis suggests that triple therapies with omeprazole are more effective than comparable regimens containing ranitidine, lansoprazole or bismuth. Omeprazole also appears to be successful in triple therapy regimens used in children with H. pylori infection. In patients with acute GORD with oesophagitis, omeprazole is at least as effective as lansoprazole or pantoprazole in promoting healing, and superior to ranitidine, cimetidine or cisapride in oesophagitis healing and symptom relief. Omeprazole was similar to lansoprazole and superior to ranitidine in preventing oesophagitis relapse in patients with all grades of oesophagitis, but may be superior to lansoprazole or pantoprazole in patients with more severe disease. More patients with symptomatic GORD without oesophagitis experienced symptom relief after short term treatment with omeprazole than with ranitidine, cisapride or placebo, and symptoms were more readily prevented by omeprazole than by cimetidine or placebo. Omeprazole was effective in healing and relieving symptoms of reflux oesophagitis in children with oesophagitis refractory to histamine H2 receptor antagonists. Omeprazole is superior to placebo in preventing NSAID-induced gastrointestinal damage in patients who must continue to take NSAIDs. It is also similar to misoprostol and superior to ranitidine in its ability to heal NSAID-induced peptic ulcers and erosions, and superior to misoprostol, ranitidine or placebo in its ability to prevent relapse. In long and short term studies, omeprazole was well tolerated, with diarrhoea, headache, dizziness, flatulence, abdominal pain and constipation being the most commonly reported adverse events. Usual omeprazole dosages, alone or combined with other agents, are 10 to 40 mg/day for adults and 10 to 20 mg/day for children. CONCLUSIONS: Omeprazole is a well studied and well tolerated agent effective in adults or children as a component in regimens aimed at eradicating H. pylori infections or as monotherapy in the treatment and prophylaxis of GORD with or without oesophagitis or NSAID-induced gastrointestinal damage.     

Omeprazole improves peak expiratory flow rate and quality of life in asthmatics with gastroesophageal reflux

OBJECTIVE: The aim of this study was to determine if omeprazole improves pulmonary function and quality of life in asthmatics with gastroesophageal reflux. METHODS: This was a double blind, randomized, placebo-controlled cross-over trial. After a 4-wk lead-in period, nine patients with documented asthma and gastroesophageal reflux, were prescribed either omeprazole 20 mg, daily or placebo for 8 wk and then crossed over to the alternate treatment. Outcome measurements included: forced expiratory volume at 1 s (FEV1), peak expiratory flow rate (PEFR), and responses on the Asthma Quality of Life Questionnaire, a validated disease specific measure of functional status. RESULTS: After omeprazole treatment, compared with placebo, patients had higher mean morning and evening PEFR, mean absolute difference (95% CI): morning: 37.8 L/min. (10.9-64.6), evening: 31.2 (3.2-59.2). Omeprazole treatment led to higher mean overall scores on the Asthma Quality of Life Questionnaire, and on the subdomains of activity limitation, symptoms, and emotions (p = 0.039, 0.049, 0.024, 0.040). A trend toward higher FEV1 (mean: 15.6% difference) with omeprazole failed to reach statistical significance (p > 0.2). CONCLUSIONS: After taking omeprazole for 8 wk, asthmatics with GER have better PEFR and quality of life than after placebo.     

Misoprostol and omeprazole in the prevention of chemotherapy-induced acute gastroduodenal mucosal injury. A randomized, placebo-controlled pilot study

BACKGROUND: Chemotherapy (CT) may induce acute mucosal injury to the stomach and duodenum, but its prevention has been scarcely investigated. METHODS: One hundred and eighty-two cancer patients with normal stomach and duodenum or having fewer than 3 erosions, selected to be treated with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) (77 breast carcinoma patients) or 5-fluorouracil (5-FU) (105 colon carcinoma patients), were randomly assigned to prophylactic treatment with misoprostol, 400 micrograms twice a day; omeprazole, 20 mg once a day; or placebo, 1 tablet twice a day. Seven days after the end of the second source of CT, all patients underwent control esophagogastroduodenoscopy. Endoscopic findings were quantified on the basis of an arbitrary score: 0 = normal; 1 = less than 3 erosions; 2 = 3-15 erosions; 3 = more than 15 erosions or ulcer; 4 = giant ulcer (greatest dimension of more than 2 cm) or multiple ulcers with cumulative greatest dimension exceeding 2 cm. RESULTS: Mean score increased significantly in the placebo and misoprostol groups, either after CMF (P < 0.001 and P < 0.05, respectively) or after 5-FU (P < 0.001 for both), whereas it did not in the omeprazole group. Gastric and duodenal ulcers were significantly less frequent in patients receiving omeprazole than in those receiving placebo (P < 0.05 after both CMF and 5-FU). No significant difference was observed between placebo and misoprostol. Omeprazole was significantly more effective than placebo and misoprostol in reducing the frequency and degree of the endoscopic worsening, either after CMF or after 5-FU (P < 0.05 for both CT regimens). Epigastric pain and/or heartburn were significantly less frequent in patients receiving omeprazole than in those receiving placebo (P < 0.01) or misoprostol (P < 0.001). CONCLUSIONS: The strong and prolonged inhibition of gastric acid production induced by omeprazole seems to be effective in preventing chemotherapy-induced gastroduodenal mucosal injury. Further trials are necessary to verify whether such a prevention of endoscopically observed injury can translate into prevention of clinically significant injury.     

Effect of omeprazole 40 mg once daily on intraduodenal and intragastric pH in H. pylori-negative healthy subjects

There is a lack of information about the effect of omeprazole or other antisecretory drugs on intraduodenal pH. Aim of the study was to document the variation over time of intraduodenal pH during a 24-hr period and to simultaneously study the effect of omeprazole 40 mg once daily on intragastric and intraduodenal pH in healthy H. pylori-negative subjects. In a randomized, placebo-controlled study, eight subjects (five women, three men, mean age 22.7 years) received oral 40 mg omeprazole or placebo once daily for eight days. On day 7, intragastric and intraduodenal pH was measured continuously for 24 hr, using two miniature glass-membrane electrodes placed in the stomach (fundus) and in the distal third of the duodenum. The 24-hr median intraduodenal pH was 5.95 with placebo and 5.85 with omeprazole. Median intragastric pH was 1.68 without and 4.93 with omeprazole. During omeprazole therapy, intragastric pH fell below 4.0 in five of eight subjects. In the 2- and 3-hr postprandial periods, the percentage of time with pH < 5 was significantly reduced with omeprazole. In healthy subjects, 24-hr median and postprandial pH in the distal part of the duodenum was lower than previously thought. Omeprazole significantly reduced the percentage of time with pH < 5 postprandially. At night, intragastric pH fell below 4.0 with omeprazole 40 mg once daily. Omeprazole does not change 24-hr median intraduodenal pH significantly.     

Twice-daily, 10-day triple therapy with omeprazole, amoxicillin, and clarithromycin for Helicobacter pylori eradication in duodenal ulcer disease: results of three multicenter, double-blind, United States trials

OBJECTIVE: We assessed the safety and efficacy of 10-day twice-daily triple therapy for Helicobacter pylori (H. pylori) in three double-blind, controlled trials in patients with duodenal ulcer disease. METHODS: H. pylori-infected patients with one or more duodenal ulcer(s) at endoscopy (studies 1, 2) or with a documented duodenal ulcer history and no duodenal ulcer or erosions at endoscopy (study 3) were randomly assigned to 10-day courses of omeprazole 20 mg b.i.d. plus amoxicillin 1 g b.i.d. plus clarithromycin 500 mg b.i.d. (OAC) or placebo plus amoxicillin 1 g b.i.d. plus clarithromycin 500 mg b.i.d. (AC). In studies 1 and 2, patients received an additional 18 days of omeprazole 20 mg q.d. (OAC group) or placebo (AC group). Endoscopy was repeated 4 wk after therapy in studies 1 and 2 and 4-6 wk after therapy in study 3. At baseline, H. pylori was diagnosed by CLOtest plus histology, or by culture. Eradication was defined as no positive biopsy test and two or more negative tests. Patients were defined as compliant if they took 75% or more of each study drug and missed < or = 3 consecutive days of the 10-day therapy. RESULTS: Intent-to-treat populations of the three studies combined were 241 patients for OAC and 266 for AC. Of all OAC patients combined, 2% stopped study medications due to adverse events, and 93% were compliant. Per-protocol cure rates were 78% to 90% (all studies combined, 84%) for OAC vs 33% to 45% (combined, 39%) for AC (p < 0.001, OAC vs AC); intent-to-treat eradication rates were 69% to 83% (combined, 75%) for OAC vs 32% to 37% (combined, 35%) for AC; (p < 0.001, OAC vs AC). CONCLUSION: Rigorously designed studies indicate that 10 days of twice-daily triple therapy with omeprazole, amoxicillin, and clarithromycin achieves per-protocol eradication rates of approximately 80% to 90% in the U.S.     

NCI? What is it? What do they do?

BACKGROUND: Omeprazole, a H+/K+ ATPase inhibitor, has been shown to reduce gastric bicarbonate secretion in cats. However, there has been no study on the effect of omeprazole on bicarbonate secretion in patients with duodenal ulcer (DU). METHODS: Fifteen men with duodenal ulcer (mean age 38 years, range 22-57) were included. Baseline gastric acid output, bicarbonate secretion, and parietal and nonparietal secretions were estimated before and after omeprazole therapy (20 mg/day) for four weeks. RESULTS: Omeprazole administration did not significantly alter bicarbonate secretion (3.3 [1.2] vs 2.4 [0.4] mmol/h), though there was significant reduction in gastric acidity (44.2 [6.6] vs 20.7 [4.6] mmol/L, p < 0.01). CONCLUSION: Omeprazole reduces acid secretion but does not affect gastric bicarbonate secretion in patients with DU.     

A comparison of omeprazole and placebo for bleeding peptic ulcer

BACKGROUND: The role of medical treatment for patients with bleeding peptic ulcers is uncertain. METHODS: We conducted a double-blind, placebo-controlled trial in 220 patients with duodenal, gastric, or stomal ulcers and signs of recent bleeding, as confirmed by endoscopy. In 26 patients the ulcers showed arterial spurting, in 34 there was active oozing, in 35 there were nonbleeding, visible vessels, and in 125 there were adherent clots. The patients were randomly assigned to receive omeprazole (40 mg given orally every 12 hours for five days) or placebo. The outcome measures studied were further bleeding, surgery, and death. RESULTS: Twelve of the 110 patients treated with omeprazole (10.9 percent) had continued bleeding or further bleeding, as compared with 40 of the 110 patients who received placebo (36.4 percent) (P<0.001). Eight patients in the omeprazole group and 26 in the placebo group required surgery to control their bleeding (P<0.001). Two patients in the omeprazole group and six in the placebo group died. Thirty-two patients in the omeprazole group (29.1 percent) and 78 in the placebo group (70.9 percent) received transfusions (P<0.001). A subgroup analysis showed that omeprazole was associated with significant reductions in recurrent bleeding and surgery in patients with nonbleeding, visible vessels or adherent clots, but not in those with arterial spurting or oozing. CONCLUSIONS: In patients with bleeding peptic ulcers and signs of recent bleeding, treatment with omeprazole decreases the rate of further bleeding and the need for surgery.     

Cortical reorganisation of sensory, motor and language functions due to early cortical damage

OBJECTIVES: To compare the pharmacokinetics and dynamics of omeprazole in white and Chinese subjects. METHODS: This double-blind two-stage study, performed in the clinical research center of a university hospital, evaluated 15 healthy nonsmoking men (eight white subjects and seven Chinese extensive metabolizers of mephenytoin). Blood samples were obtained over 24 hours after the eighth omeprazole dose (40 mg/day). Omeprazole, omeprazole sulfone, and hydroxyomeprazole pharmacokinetics were calculated from the respective plasma concentration-time curves. Twelve- and 24-hour integrated plasma gastriun (AUCgas12 and AUCgas24) were calculated from the respective plasma gastrin concentrations. A week before the initiation of omeprazole the activities of CYP2D6, CYP2C19, and CYP3A4 were determined by previously established methods. RESULTS: Omeprazole concentrations were significantly lower (mean area under the plasma concentration time curve extrapolated to infinity [AUCO-infinity] +/- SEM; 7.53 +/- 1.21 versus 12.80 +/- 2.13 mumol.hr.L-1, respectively; p < 0.05) and its oral clearance greater (319 +/- 60 versus 183 +/- 35 ml/min, respectively; p < 0.05) in the white subjects than in the Chinese subjects. Omeprazole and omeprazole sulfone AUCO-infinity values were well correlated with the S/R mephenytoin ratio (r = 0.82 and r = 0.84, respectively; p < 0.001) and with urinary 4'-hydroxymephenytoin (r = -0.58 [p < 0.03] and r = -0.52 [p < 0.02], respectively). Fasting gastrin, AUCgas12, and AUCgas24 were significantly greater in the Chinese subjects than in the white subjects (30.0 +/- 6.4 versus 14.4 +/- 1.2 pmol, respectively [p < 0.02]; 661 +/- 114 versus 334 +/- 38 pmol.hr.L-1, respectively [p < 0.002]; and 1414 +/- 228 versus 747 +/- 99 pmol.hr.L-1, respectively [p < 0.004]). In addition, the S/R mephenytoin ratio and omeprazole AUCO-infinity correlated with the extent of omeprazole induced hypergastrinemia. CONCLUSION: The metabolism of omeprazole and the rise in gastrin concentration after its administration is genetically determined and ethnically dependent.     

Omeprazole treatment of chronic duodenal ulceration

Omeprazole, a substituted benzimidazole, is an acid pump inhibitor, introduced for treatment of chronic duodenal ulceration. In a study of 116 patients with endoscopically documented chronic duodenal ulcers, omeprazole affected healing in 77 (66.3%) patients after two weeks and 106 (91.4%) patients after four weeks, with symptoms relief in 102 (88%) patients within the first week of treatment. There was significantly higher healing rate in females (p < 0.05) and diffuse ulceration rather than single ulcers (p < 0.05). In meta-analysis comparing omeprazole to other antiulcer drugs reported in this country, there was a significant higher healing rate (p < 0.01) and symptom relief (p < 0.01) in favour of omeprazole. It proved to be effective and safe for the short term treatment of chronic duodenal ulceration.     

Control of bacterial infections in the hard tick Dermacentor variabilis (Acari: Ixodidae): evidence for the existence of antimicrobial proteins in tick hemolymph

AIMS: To investigate the efficacy of daily maintenance treatment with omeprazole 10 mg in reducing the relapse rate of healed erosive oesophagitis. METHODS: Three hundred patients with erosive oesophagitis (grade 2 or greater) received omeprazole 20 mg daily for 12 weeks, followed by 40 mg daily for a further 12 weeks if required. After healing, patients were randomised to double blind treatment with omeprazole 10 mg daily or placebo for up to 18 months. On relapse the treatment cycle was repeated. RESULTS: The cumulative healing rate at 12 weeks in the initial healing period was 95%, and 96% and 98% on rehealing courses after relapse in the first and second maintenance periods respectively. After 12 weeks of treatment, 98% of patients were free from heartburn and 97% were free of all reflux related symptoms. Relapse in the subgroup of patients who relapsed in both maintenance periods was infrequent on omeprazole 20 mg daily: only 9% at two years. Gastrin concentrations rose above normal in one third of patients. One patient had linear hyperplasia of endocrine cells and another had micronodular hyperplasia. There were no side effects definitely attributable to omeprazole. CONCLUSION: Maintenance treatment with omeprazole 10 mg daily keeps about 60% of patients with erosive oesophagitis in prolonged remission. Patients relapsing once are likely to do so again; they can subsequently be treated effectively with omeprazole 20 mg daily.     

Helicobacter pylori does not migrate from the antrum to the corpus in response to omeprazole

BACKGROUND: Omeprazole is known to have an effect on Helicobacter pylori in vivo. One opinion is that H. pylori "migrates" from the antrum to the corpus in response to omeprazole therapy. METHODS: To determine whether H. pylori migrates in response to omeprazole, we assessed the presence of H. pylori in the antrum and corpus in duodenal ulcer patients receiving omeprazole for 4 wk. Culture and histological examination of antral biopsies (Genta stain) were performed before patients received omeprazole, at the end of therapy, and 4-6 wk later. The end points were presence or absence of H. pylori and the number of H. pylori colonies per biopsy. RESULTS: Seventy-two patients had H. pylori in both the antrum and corpus at entry and 4-6 wk after ending therapy. Three general patterns were prevalent at the end of omeprazole therapy: antrum- and corpus-positive (54%), antrum-negative and corpus-positive (24%), both antrum- and corpus-negative (21%), and one patient had antrum-positive with corpus-negative (1%). Evaluation of the number of colonies per biopsy in those who remained H. pylori-positive in both the antrum and corpus throughout showed that the number of H. pylori decreased in both the antrum and corpus during therapy (507 +/- 60 vs. 225 +/- 51, p < 0.01 and 415 +/- 58 vs. 290 +/- 46 0.1) for antrum and corpus, respectively, and tended to return to pre-therapy levels 4-6 wk later. The number of H. pylori in the corpus also decreased in the antrum-negative and corpus-positive group during therapy with omeprazole (433 +/- 87 vs. 185 +/- 61, p < 0.05). In most of the patients studied, the number of H. pylori in the corpus was less posttreatment than it was pretreatment. The decrease in H. pylori load was also reflected in the development of false-negative urea breath tests. CONCLUSIONS: Omeprazole is detrimental to H. pylori in both the antrum and the corpus; migration from the antrum to the corpus in response to omeprazole is a myth.     

Comparative effects of omeprazole on xenobiotic metabolizing enzymes in the rat and human

Omeprazole induces CYP1A in the human liver and gut, which has led to concern about possible side effects. The purpose of this study was to compare the effects of omeprazole on phase 1 and phase 2 enzymes in the rat and human. Male rats were treated with intraperitoneal (40 or 80 mg/kg) or oral omeprazole (40 mg/kg) for 5 or 14 days, respectively. The activities and amounts of CYP1A, uridine diphosphate-glucuronosyltransferase, and glutathione transferase were determined in liver and gut. Enzyme activities were also determined in duodenal biopsy specimens from six healthy human volunteers before and after treatment with omeprazole (20 mg/day) for 10 days. Treatment with intraperitoneal omeprazole (40 mg/kg; 80 mg/kg) coinduced uridine diphosphate-glucuronosyltransferase (36%; 66%), glutathione transferase (22%; 50%), and CYP1A (26%; 50%) in rat liver. In rat small intestine, comparable levels of induction were observed for uridine diphosphate-glucuronosyltransferase and glutathione transferase; CYP1A was unaffected. Oral omeprazole had similar effects. Immunoblotting showed corresponding changes in the amounts of these enzymes. Omeprazole increased the activities of CYP1A (19% to 167%; p = 0.014) and uridine diphosphate-glucuronosyltransferase (11% to 68%; p = 0.04) in the duodenal biopsy specimens of all six human volunteers; glutathione transferase was unaffected. Thus, omeprazole coinduced multiple xenobiotic metabolizing enzymes in the rat and human. The pattern of induction differed in the rat and human, consistent with known differences in genetic regulatory elements in the two species.     

Comparison of the effect of two dose schedules of oral omeprazole with oral ranitidine on gastric aspirate pH and volume in patients undergoing elective surgery

We have compared gastric aspirate pH and volume at induction of anaesthesia in 222 patients who had received either omeprazole or ranitidine before elective operations. Omeprazole was given orally either as 40 mg on the evening before and 40 mg on the morning of surgery or as 80 mg on the morning of surgery. Ranitidine 150 mg was given orally on the evening before surgery and 2 h before anaesthesia. Treatment success was defined as aspirate pH > or = 2.5 and volume < 25 ml at induction of anaesthesia. Treatment was successful in 84% (95% confidence interval (CI) 73-91%) of patients in the omeprazole 40 + 40 mg group, 84% (95% CI 73-91%) in the ranitidine group and 73% (95% CI 61-83%) in the omeprazole 80 mg group. There were no statistically significant differences between the groups. Twelve patients in the omeprazole 80 mg group had gastric pH < 2.5 and four had volume > 25 ml. Only three patients had a gastric pH < 2.5 in the omeprazole 40 + 40 mg group and none had volume > 25 ml, which compared well with the ranitidine group. Omeprazole, given as 40 mg in the evening and 40 mg on the morning of operation, has a potential role for use in patients at risk for aspiration during general anaesthesia.     

Can optimal acid suppression prevent rebleeding in peptic ulcer patients with a non-bleeding visible vessel: a preliminary report of a randomized comparative study

BACKGROUND/AIMS: The hypothesis that profound acid suppression might prevent clot lysis and thus benefit patients with a non-bleeding visible vessel has not been confirmed. Omeprazole can suppress gastric acid remarkably and may be beneficial for patients with peptic ulcer bleeding. METHODOLOGY: Fifty-two patients with a non-bleeding visible vessel at the ulcer base were enrolled and randomized into four groups (N = 13 in each group). In the cimetidine group, the patients received cimetidine 300 mg i.v. bolus followed by 300 mg i.v. every 6 hr during hospitalization. In the heater probe thermocoagulation + cimetidine group, the patients received heater probe thermocoagulation and cimetidine 300 mg i.v. bolus followed by 300 mg i.v. every 6 h during hospitalization. In the omeprazole q.d. group, the patients received omeprazole 40 mg i.v. bolus followed by 40 mg i.v. daily for two days. In the omeprazole q 12 h group, the patients received omeprazole 40 mg i.v. bolus followed by 40 mg i.v. every 12 h for two days. A 24 hr intragastric pH was recorded for every case. RESULTS: The mean 24 hr intragastric pH were higher in the omeprazole q.d. (mean 5.8) and the omeprazole q 12 h groups (mean 6.4) than in the cimetidine (mean 4.3) and the heater probe thermocoagulation + cimetidine groups (mean 4.9) (p < 0.05). Rebleeding occurred in 5, 2, 2 and 2 patients in the cimetidine, heater probe thermocoagulation + cimetidine, omeprazole q.d., and omeprazole q 12 h groups, respectively (p > 0.05). Volume of blood transfusion and number of days in hospital were not statistically different among the four groups. CONCLUSIONS: Omeprazole can remarkably suppress gastric acid when it is compared to that of the H2 receptor blocker. Patients with a non-bleeding visible vessel using omeprazole do not exhibit a decrease in the rebleeding rate as compared with those patients using cimetidine.     

"Eight drugs in one day" chemotherapy in a nonfamilial bilateral retinoblastoma with recurrent cerebrospinal fluid metastases

OBJECTIVE: To evaluate whether the addition of bismuth subnitrate to a dual oral therapy regimen with omeprazole plus amoxycillin could improve Helicobacter pylori eradication. METHODS: Fifty consecutive Helicobacter pylori-positive patients were randomly enrolled to receive either (A) bismuth subnitrate (300 mg q.d.s.), omeprazole (20 mg b.d.) and amoxycillin (500 mg q.d.s.), or (B) omeprazole (20 mg b.d.) and amoxycillin (500 mg q.d.s.). Both groups (n=25 each) received the medication for 14 days. H. pylori status was reassessed 30 days after completion of the therapy in order to evaluate eradication rates. RESULTS: Six patients were lost to follow-up and therefore excluded from the study (three patients from each group). One patient from Group B withdrew from the study because of side-effects. The addition of bismuth subnitrate to omeprazole and amoxycillin significantly improved its efficacy in eradicating H. pylori, with 72% (18/25) eradication in Group A and 52% (13/25) in Group B (P=0.027). The addition of bismuth subnitrate to dual oral therapy was also capable of improving the healing of peptic ulcers when compared with dual oral therapy alone (100%, 8/8 vs. 58%, 4/7; P=0.021). CONCLUSION: Our results demonstrate that the addition of bismuth subnitrate to dual oral therapy enhances H. pylori eradication, and improves healing of peptic ulcers.     

Dormancy-associated gene expression in pea axillary buds. Cloning and expression of PsDRM1 and PsDRM2

OBJECTIVE: We evaluated the efficacy and safety of a twice-daily dosage regimen of cisapride 20 mg in relieving the symptoms of mild-moderate gastroesophageal reflux disease (GERD) in patients with moderate intensity heartburn and no history of erosive esophagitis. METHODS: After a 2-wk, single-blind, placebo run-in period, 398 patients who continued to experience moderate intensity heartburn were randomized to either placebo (n = 196) or cisapride 20 mg (n = 202) twice daily for 4 wk. RESULTS: Compared with placebo, cisapride significantly reduced scores for daytime and nighttime heartburn (p < 0.001), total regurgitation (p < 0.001), eructation (p = 0.04), and early satiety (p = 0.04). Cisapride 20 mg b.i.d. was also superior to placebo in reducing total use of rescue antacid medication (p < 0.001); reducing, in concordance analyses, daytime and nighttime heartburn with antacid usage (p < 0.001); increasing the percentage of heartburn-free days and antacid-free nights (p < 0.5); and increasing the percentage of patients self-rated as having minimal or better symptomatic improvement (p = 0.01). Cisapride 20 mg b.i.d. was well tolerated. The most common adverse event in the cisapride group was diarrhea, reported by 10% of patients, compared with an incidence of 4% in the placebo group. CONCLUSION: Cisapride 20 mg b.i.d. was shown to be effective and safe for the short-term treatment of daytime and nighttime heartburn and for other symptoms associated with mild-moderate GERD.     

Ranitidine controls nocturnal gastric acid breakthrough on omeprazole: a controlled study in normal subjects

BACKGROUND & AIMS: Proton pump inhibitors administered twice daily do not provide complete nocturnal acid suppression. Acid breakthrough, or decrease in intragastric pH to <4 for an hour or longer, occurs in three quarters of normal subjects and patients at night. We compared the effect of a third dose of omeprazole at bedtime with that of a dose of ranitidine at bedtime on residual nocturnal acid secretion in patients receiving omeprazole twice daily. METHODS: Twelve volunteers underwent overnight intragastric pH monitoring after 7 days of treatment with omeprazole, 20 mg twice daily, followed by different treatment supplements at bedtime: placebo; additional omeprazole, 20 mg; ranitidine, 150 mg; and ranitidine, 300 mg. RESULTS: Additional omeprazole at bedtime reduced the percentage of time with intragastric pH of <4 from 48% to 31% (P < 0.005) compared with omeprazole twice daily with placebo at bedtime. Ranitidine at bedtime reduced this parameter more, 5% with 150 mg and 6% with 300 mg (P <0.01 vs. omeprazole twice daily plus bedtime). Results for percentage of time with intragastric pH <3 were similar. Eleven subjects had acid breakthrough with placebo at bedtime; 7 with omeprazole at bedtime (P = NS); 4 with ranitidine, 150 mg at bedtime; and 3 with ranitidine, 300 mg at bedtime (P < 0. 05, ranitidine vs. placebo). CONCLUSIONS: Bedtime ranitidine is more effective than bedtime omeprazole on residual nocturnal acid secretion in patients receiving omeprazole twice daily. This finding suggests that fasting breakthrough nocturnal acid secretion in patients receiving omeprazole twice daily is most likely histamine related.     

Neutrophils, Helicobacter pylori, and nonsteroidal anti-inflammatory drug ulcers

BACKGROUND & AIMS: Gastric injury by nonsteroidal anti-inflammatory drugs (NSAIDs) is minimal in neutropenic animals. This study examined peptic ulcer development in the presence or absence of gastric neutrophils in patients requiring long-term use of NSAIDs. METHODS: Gastric histology, neutrophils, and Helicobacter pylori were assessed in 120 patients randomized to receive placebo or 20 or 40 mg famotidine twice daily as prophylaxis against NSAID-related ulcers and who underwent endoscopy at 0, 4, 12, and 24 weeks. RESULTS: In 43 patients without gastric neutrophils, ulcers developed in 1 of 14 (7.7%) taking placebo, 2 of 16 (12.5%) taking 20 mg famotidine, and none of 13 taking 40 mg famotidine. However, in 77 patients with neutrophils, ulcers developed in 13 of 28 (47. 4%) taking placebo (P < 0.001), 3 of 26 (12.6%) taking 20 mg famotidine, and 3 of 23 (13%) taking 40 mg famotidine. Eight of 46 patients (17%) without H. pylori had neutrophils compared with 69 of 74 (93%) with both H. pylori and neutrophils (P < 0.001). CONCLUSIONS: Gastric neutrophils increase the incidence of ulceration in long-term NSAID users. Because neutrophils exist with H. pylori, eradicating this infection might prevent NSAID-related peptic ulcers.     

Health-related quality of life outcomes of omeprazole versus ranitidine in poorly responsive symptomatic gastroesophageal reflux disease

OBJECTIVE: This study evaluated changes in health-related quality of life (HRQL) outcomes of once-daily omeprazole compared with ranitidine for the short-term treatment of patients with poorly responsive symptomatic gastroesophageal reflux disease (GERD). METHODS: A double-blind, randomized clinical trial, compared omeprazole versus ranitidine for the treatment of poorly responsive GERD. Eligible patients had a history of predominant heartburn symptoms with symptomatic heartburn after 6 weeks of ranitidine treatment. Patients were randomized to omeprazole 20 mg once daily (n = 156) or ranitidine 150 mg twice daily (n = 161) and followed for 8 weeks. Assessments were completed at baseline and after 8 weeks with physician-rated symptoms: Gastrointestinal Symptom Rating Scale (GSRS); Psychological General Well-Being (PGWB) Index; Sleep Scale; Impact on Daily Activities Scale, and Overall Treatment Effect. Primary HRQL endpoints were the GSRS reflux scale and PGWB total score. RESULTS: No differences between the 2 treatment groups were observed in baseline demographic, clinical or HRQL measures. After 8 weeks, omeprazole-treated patients had greater improvement in GSRS reflux scale scores (p<0.0001) and PGWB total scores (p = 0. 019) compared with ranitidine-treated patients. Significant between group differences favoring omeprazole were also observed in GSRS total scores (p<0.0001), abdominal pain scale scores (p = 0.003), and indigestion scale scores (p = 0.003), Impact on Daily Activities (p = 0.001), PGWB positive well-being (p = 0.015), anxiety (p = 0. 030), and general health scale scores (p = 0.010). Patient ratings of overall treatment effect demonstrated the significantly (p<0. 0001) greater benefits of omeprazole (mean = 5.26) compared with ranitidine treatment (mean = 3.83). CONCLUSIONS: Omeprazole treatment significantly reduced persistent reflux-related symptoms and normalized psychological well-being compared with ranitidine in poorly responsive symptomatic patients with GERD.     

Enhancement of morphine antinociception by ibogaine and noribogaine in morphine-tolerant mice

BACKGROUND: The authors evaluated and compared the efficacy of 20 mg versus 40 mg of paroxetine in a randomized, double-blind, parallel-group study during a maintenance period of 28 months. METHOD: Ninety-nine inpatients with recurrent, unipolar depression (DSM-IV criteria) who had at least 1 depressive episode during the 18 months preceding the index episode were openly treated with paroxetine 40 mg/day. Seventy-two subjects had a stable response (Hamilton Rating Scale for Depression score < 8) to paroxetine treatment and remained in the continuation treatment as outpatients for 4 months. At the time of recovery, 68 patients were randomly assigned to 1 of the 2 maintenance treatment groups: paroxetine 20 mg or paroxetine 40 mg daily. RESULTS: Sixty-seven patients completed the 28-month follow-up period. Seventeen (51.5%) of 33 patients in the 20-mg paroxetine regimen had a single recurrence compared with 8 (23.5%) of 34 subjects in the 40-mg dose regimen (chi2 = 5.56, p = .018). CONCLUSION: These data suggest that a full dose of paroxetine is recommended in unipolar patients who are at high risk for recurrent depressive episodes.