Disturbed bowel habits in patients with non-ulcer dyspepsia

BACKGROUND; Emerging medications for non-ulcer-dyspepsia, such as the serotonin-receptor modulators, also affect bowel habits by altering colonic transit. If drugs that alter colonic function were to prove useful in non-ulcer dyspepsia, knowledge of baseline bowel habit disturbances would be potentially critical. AIM: To estimate the rate of non-ulcer dyspepsia patients with clinically relevant constipation or diarrhoea potentially precluding use of motility agents. METHODS: Consecutive patients with non-ulcer dyspepsia (n = 79), gastro-oesophageal reflux disease (n = 135) and organic upper gastrointestinal disease (upper gastrointestinal disease; n = 36) completed a validated symptom questionnaire evaluating predominant bowel habits in the last year. RESULTS: Prevalence of constipation was higher in non-ulcer dyspepsia (34%) than in gastro-oesophageal reflux disease (P = 0.01) and organic upper gastrointestinal disease (P = 0.01), prevalence of alternating diarrhoea/constipation (24%) and diarrhoea (22%) was similar, while prevalence of normal bowel habits was significantly less in non-ulcer dyspepsia (20%; P = 0.01 vs. gastro-oesophageal reflux disease and P < 0.01 vs. organic upper gastrointestinal disease). Constipation was particularly frequent in ulcer-like and dysmotility-like non-ulcer dyspepsia, while prevalence of diarrhoea was lowest in dysmotility-like non-ulcer dyspepsia. A normal bowel habit was equally uncommon in male (21%) and female non-ulcer dyspepsia patients (20%). CONCLUSIONS: Only one of five non-ulcer dyspepsia patients had normal bowel habits based on clinical symptoms; constipation is particularly prevalent. Patients with functional dyspepsia who are prescribed motility altering drugs should be evaluated by taking a thorough bowel habit history.     

Arrest of chronic acid suppressant drug use after successful Helicobacter pylori eradication in patients with peptic ulcer disease: a six-month follow-up study

BACKGROUND: It remains controversial whether successful H. pylori eradication leads to relief of dyspepsia and the subsequent arrest or tapering of acid-suppressant drug therapy, or to an aggravation of acid-related dyspepsia requiring more acid-suppressant drug intake. AIM: To evaluate prospectively the effect of H. pylori eradication on the requirement of acid-suppressant drug or antacids and the evolution of dyspeptic symptoms in chronic acid-suppressant drug users with peptic ulcer disease. MATERIALS AND METHODS: The use of acid-suppressant drugs, rescue antacids and predominant symptoms were recorded prospectively during 24 weeks after H. pylori eradication therapy in 75 peptic ulcer disease patients. RESULTS: In 71 patients with complete follow-up, ulcers were healed at follow-up endoscopy and H. pylori was successfully eradicated. After 6 months, 93% (66 out of 71) of chronic acid-suppressant drug users had stopped acid-suppressant drug intake. The mean daily acid-suppressant drug dosage per patient decreased from 1.72 at entry to 0.03 units acid-suppressant drug (98%; P < 0.0001) during follow-up. The mean number of antacid tablets/day/patient was 0.26 during follow-up for the relief of mild inter-current dyspeptic symptoms. Medication use was not different in peptic ulcer disease patients with or without gastro-oesophageal reflux disease at baseline. The prevalence of gastro-oesophageal reflux disease decreased from 42% before to 35% after H. pylori eradication (N.S.). CONCLUSION: Successful H. pylori eradication in peptic ulcer disease patients almost completely eliminates the need for acid-suppressant drug regardless of the presence or absence of gastro-oesophageal reflux disease at entry.     

Helicobacter pylori infection--current treatment practice

Helicobacter pylori infection, which is present in 30 - 60% of the population in developed countries and in more than 60% in developing countries, is established to be a major cause of gastritis, peptic ulcer disease and gastric cancer. Eradication therapy has been incorporated into clinical practice over the past 15 years. Treatment regimens include a 2 week bismuth-based triple therapy (a bismuth compound plus metronidazole, tetracycline or amoxycillin), a 1 week proton-pump inhibitor (PPI)-based triple therapy and a 1 week ranitidine bismuth citrate (RBC)-based triple therapy (a PPI or RBC plus any two of the three antibiotics, metronidazole, amoxycillin and clarithromycin). These regimens achieve eradication rates of > 80%. H. pylori resistance to metronidazole and clarithromycin decreases the clinical efficacy of most regimens, despite the high eradication rates for resistant strains achieved by the RBC-triple therapy in some recent trials. The dose of antibiotics (especially clarithromycin) and the duration of treatment may also influence the eradication rate. Doctors' beliefs impact on clinical practice and, thus, influence the clinical application of eradication therapy. Whereas peptic ulcer disease and primary gastric low-grade B-cell mucosa-associated lymphoid tissue lymphoma (MALToma) have become established as definite indications for eradication therapy, there remain controversies surrounding non-ulcer dyspepsia, gastro-oesophageal reflux disease, atrophic gastritis, intestinal metaplasia, use of non-steroidal anti-inflammatory drugs (NSAIDs) and H. pylori-related extradigestive diseases.     

Helicobacter pylori infection - current treatment practice

Helicobacter pylori infection, which is present in 30 - 60% of the population in developed countries and in more than 60% in developing countries, is established to be a major cause of gastritis, peptic ulcer disease and gastric cancer. Eradication therapy has been incorporated into clinical practice over the past 15 years. Treatment regimens include a 2 week bismuth-based triple therapy (a bismuth compound plus metronidazole, tetracycline or amoxycillin), a 1 week proton-pump inhibitor (PPI)-based triple therapy and a 1 week ranitidine bismuth citrate (RBC)-based triple therapy (a PPI or RBC plus any two of the three antibiotics, metronidazole, amoxycillin and clarithromycin). These regimens achieve eradication rates of >> 80%. H. pylori resistance to metronidazole and clarithromycin decreases the clinical efficacy of most regimens, despite the high eradication rates for resistant strains achieved by the RBC-triple therapy in some recent trials. The dose of antibiotics (especially clarithromycin) and the duration of treatment may also influence the eradication rate. Doctors’ beliefs impact on clinical practice and, thus, influence the clinical application of eradication therapy. Whereas peptic ulcer disease and primary gastric low-grade B-cell mucosa-associated lymphoid tissue lymphoma (MALToma) have become established as definite indications for eradication therapy, there remain controversies surrounding non-ulcer dyspepsia, gastro-oesophageal reflux disease, atrophic gastritis, intestinal metaplasia, use of non-steroidal anti-inflammatory drugs (NSAIDs) and H. pylori-related extradigestive diseases.     

Strategy for treatment of Helicobacter pylori infection in adults. I. Updated indications for test and eradication therapy suggested in 2000

Since the report of culture of Helicobacter pylori in 1983, there has been increasing agreement that H. pylori infection is etiologically associated with a number of important diseases including chronic active gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, gastric polyps, gastric cancer, as well as suggestions that it may be involved in diseases outside the upper gastrointestinal tract. There have been a number of national and international consensus meetings to propose guidelines to treat H. pylori infection. The recommendations of these conferences are reviewed here and updated to include new indications and concepts regarding H. pylori eradication therapy. Eradication therapy is considered the standard of care for active or inactive peptic ulcer patients including those who use non-steroidal anti-inflammatory drugs (NSAIDs). Other strong indications include MALT lymphoma, hyperplastic polyps, hyperplastic gastropathy, post-endoscopic resection for gastric malignancy, and acute H. pylori gastritis. Other considerations include plan to use chronic NSAID therapy, plan for chronic anti-secretory therapy, and some extra-gastroduodenal diseases such as chronic ureterica. Non-investigated dyspepsia is an indication for diagnostic evaluation and eradication therapy for those with H. pylori infection, whereas non-ulcer dyspepsia (NUD) in which peptic ulcer disease has been excluded is not an indication for evaluation per se. Intervention studies are now in progress to test the hypothesis that prevention of gastric malignancy is an outcome of H. pylori eradication. Because the prevalence of H. pylori infection and the associated diseases such as peptic ulcer or gastric cancer differ among countries as well as different approvals for treatment are required by governments or insurance agencies, the acceptable indications of eradication therapy will, by necessity, vary among countries.     

Personal view: to treat or not to treat? Helicobacter pylori and gastro‐oesophageal reflux disease — an alternative hypothesis

Helicobacter pylori causes acute on chronic gastritis and is responsible for most peptic ulcers and gastric cancer. However, recent papers have suggested that it may protect against gastro-oesophageal reflux, Barrett's oesophagus and oesophageal cancer. Furthermore, the rapid increase in gastro-oesophageal reflux disease, Barrett's oesophagus and adenocarcinoma of the oesophagus in the developed world has been attributed by some to the falling prevalence of H. pylori. These considerations have led to the suggestion that H. pylori infection should not necessarily be treated, especially in patients with gastro-oesophageal reflux disease. Conversely, data from prospective randomized studies have shown that H. pylori eradication does not cause gastro-oesophageal reflux disease in patients with duodenal ulcer or in the normal population, nor does it worsen the outcome of pre-existing gastro-oesophageal reflux disease. Therefore, although H. pylori is negatively associated with gastro-oesophageal reflux disease, its eradication does not induce the disease. A hypothesis is presented suggesting that the increased prevalence of gastro-oesophageal reflux disease is a result of rising acid secretion in the general population, which, in turn, is a consequence of the increased linear height (a predictor of acid secretion). The greater acid secretion could also explain the decline in the prevalence of H. pylori and perhaps account for the inverse relationship between H. pylori and gastro-oesophageal reflux disease. These considerations are explored in discussing whether H. pylori infection should be treated in infected patients presenting with gastro-oesophageal reflux disease.     

Sucralfate gel versus placebo in patients with non-erosive gastro- oesophageal reflux disease.

BACKGROUND: Gastro-oesophageal reflux disease, a term used to refer to chest symptoms that result from reflux of gastric acid into the oesophagus, occur at least daily in 7% and every 3 days in 33% of the population. METHODS: One hundred and forty-one patients with moderate to severe gastro-oesophageal reflux symptoms occurring at least three times per week (but no oesophageal erosions or ulcers at endoscopy) were treated in this randomized, double-blind, placebo-controlled study at six trial centres. Treatment was given for 6 weeks and consisted of daily doses of either 1 g sucralfate gel b.d. or placebo. The evaluation of efficacy was based on data of 139 patients. RESULTS: The responder rate at Day 42 was statistically significantly higher for the patients treated with sucralfate (71%) than for the placebo patients (29%) (P < 0.0001, Fisher's exact test). The overall response of the non-ulcer dyspepsia and gastro-oesophageal reflux disease symptoms was better for sucralfate gel than for placebo with 45% of patients treated with sucralfate gel being considered as having a 'good' or 'excellent' overall response compared with 22% of the patients who received placebo (P < 0.0001, Wilcoxon test). Only a few adverse experiences were reported by 10% of sucralfate patients and 7% of placebo patients. CONCLUSION: In this trial, we demonstrated a statistically significant superiority of sucralfate gel at a dosage of 1 g b.d. compared to placebo in the treatment of patients with gastro-oesophageal reflux disease. Sucralfate gel was well tolerated.     

Is Helicobacter pylori relevant in the management of reflux disease?

Data on the interaction of reflux disease and Helicobacter pylori infection are limited in scope and rigour, controversial and difficult to interpret. Despite this, a framework of understanding is emerging, which is consistent with known effects on gastric acid secretion.
In patients with moderate to severe H. pylori -induced corpus gastritis, eradication can increase substantially impaired gastric acid secretion sufficiently to precipitate reflux disease in people with pre-existing sub-clinical defective gastro-oesophageal competence. By contrast, reflux disease in duodenal ulcer patients probably benefits from eradication of H. pylori . There appears to be no significant impact on reflux disease from eradication in healthy subjects or individuals whose primary problem is reflux disease.
Helicobacter pylori -infected reflux disease patients respond slightly better to proton pump inhibitors. These agents cause a topographic alteration of gastritis from antrum to corpus, the clinical significance of which is controversial.
Many practitioners misjudge the risks and benefits of the effects of H. pylori eradication on reflux disease. Regardless of patient diagnosis, the balance is in favour of H. pylori eradication. For those in whom reflux oesophagitis development is a defined possibility, oesophagitis is mild, easily treated and most unlikely to be associated with any major risk for development of oesophageal adenocarcinoma.     

Current concepts in the management of Helicobacter pylori infection--the Maastricht 2-2000 Consensus Report

Significant progress and new insights have been gained in the 4 years since the first Maastricht Consensus Report, necessitating an update of the original guidelines. To achieve this, the European Helicobacter Pylori Study Group organized a meeting of specialists and experts from around the world, representatives from National Gastroenterology Societies and general practitioners from Europe to establish updated guidelines on the current management of Helicobacter pylori infection. The meeting took place on 21-22 September 2000. A "test and treat" approach is recommended in adult patients under the age of 45 years (the age cut-off may vary locally) presenting in primary care with persistent dyspepsia, having excluded those with predominantly gastro-oesophageal reflux disease symptoms, non-steroidal anti-inflammatory drug users and those with alarm symptoms. Diagnosis of infection should be by urea breath test or stool antigen test. As in the previous guidelines, the eradication of H. pylori is strongly recommended in all patients with peptic ulcer, including those with complications, in those with low-grade gastric mucosa-associated lymphoid tissue lymphoma, in those with atrophic gastritis and following gastric cancer resection. It is also strongly recommended in patients who are first-degree relatives of gastric cancer patients and according to patients' wishes after full consultation. It is advised that H. pylori eradication is considered to be an appropriate option in infected patients with functional dyspepsia, as it leads to long-term symptom improvement in a subset of patients. There was consensus that the eradication of H. pylori is not associated with the development of gastro-oesophageal reflux disease in most cases, and does not exacerbate existing gastro-oesophageal reflux disease. It was agreed that the eradication of H. pylori prior to the use of non-steroidal anti-inflammatory drugs reduces the incidence of peptic ulcer, but does not enhance the healing of gastric or duodenal ulcer in patients receiving antisecretory therapy who continue to take non-steroidal anti-inflammatory drugs. Treatment should be thought of as a package which considers first- and second-line eradication therapies together. First-line therapy should be with triple therapy using a proton pump inhibitor or ranitidine bismuth citrate, combined with clarithromycin and amoxicillin or metronidazole. Second-line therapy should use quadruple therapy with a proton pump inhibitor, bismuth, metronidazole and tetracycline. Where bismuth is not available, second-line therapy should be with proton pump inhibitor-based triple therapy. If second-line quadruple therapy fails in primary care, patients should be referred to a specialist. Subsequent failures should be handled on a case-by-case basis by the specialist. In patients with uncomplicated duodenal ulcer, eradication therapy does not need to be followed by further antisecretory treatment. Successful eradication should always be confirmed by urea breath test or an endoscopy-based test if endoscopy is clinically indicated. Stool antigen test is the alternative if urea breath test is not available.     

Effects of antacid formulation on postprandial oesophageal acidity in patients with a history of episodic heartburn

BACKGROUND: Heartburn self-treatment with antacids is extremely common. If the oesophagus is the primary site of antacid action, chewable antacids might raise the oesophageal pH more effectively than swallowable tablets. AIM: To establish a model to assess postprandial acid reflux and to compare the onset and duration of action on oesophageal pH of different antacid formulations. METHODS: Twenty subjects with a history of episodic heartburn underwent eight pH monitoring sessions each for 5.5 h postprandially. One hour after consuming a meal consisting of chili, cheese, raw onions and cola, subjects received 750 mg, 1500 mg and 3000 mg of either chewable or swallowable CaCO3 tablets, an effervescent bicarbonate solution or placebo. Oesophageal and gastric pH data were collected. RESULTS: Mean intra-oesophageal pH remained lower than baseline for more than 1 h (pH range 5-5.5) postprandially, indicating reflux of somewhat acidic intragastric contents into the oesophagus. The onset of action on oesophageal pH was similar for all antacids (30-35 min). The duration of action on pH varied: chewable tablets and effervescent bicarbonate had relatively long durations of action (oesophagus, 40-45 min; stomach, 100-180 min); swallowable tablets had little effect. CONCLUSIONS: The meal model used in this study dependably produced acidic gastro-oesophageal reflux. Antacids increased oesophageal pH independent of gastric pH, demonstrating that chewing antacids controls oesophageal acidity more effectively than swallowing antacid tablets.     

Review article: an approach to Helicobacter pylori infection in the elderly

The prevalence of Helicobacter pylori infection increases with age world-wide, reaching levels of 40-60% in asymptomatic elderly subjects and over 70% in elderly patients with gastroduodenal diseases. However, the percentage of H. pylori-positive elderly patients who are treated for their infection remains very low. Data are now available that demonstrate the benefit of curing H. pylori infection in elderly patients with H. pylori-associated peptic ulcer disease and severe chronic gastritis. Furthermore, the cure of H. pylori may prevent the progression of intestinal metaplasia and gastric atrophy. New studies are needed to clarify the role of eradication in elderly patients with non-ulcer dyspepsia and gastro-oesophageal reflux disease and in those who use non-steroidal anti-inflammatory drugs. H. pylori infection may be easily diagnosed by histological evaluation, rapid urease test or culture performed on gastric biopsies taken during endoscopy. However, the biopsy site must be carefully selected in elderly patients. For non-invasive monitoring of H. pylori infection after treatment, the 13C-urea breath test has significantly higher accuracy than serology in the elderly; further studies are needed to clarify the role of the H. pylori stool antigen test in old age. One-week proton pump inhibitor-based triple therapy regimens, including clarithromycin, amoxicillin and/or nitroimidazoles, are highly effective and well tolerated in elderly patients. Low doses of both proton pump inhibitors and clarithromycin (in combination with standard doses of amoxicillin or nitroimidazoles) are sufficient. Low compliance and antibiotic resistance are the main factors related to treatment failure in old age.     

Mosapride in gastrointestinal disorders

Mosapride was effective in improving overall symptoms in patients with gastrointestinal disorders, including chronic gastritis, gastro-oesophageal reflux disease and functional dyspepsia. Mosapride was more effective than teprenone in improving gastric stasis symptoms and gastric pain after 2 weeks of therapy (p < 0.001) in an open-label trial in 1042 patients with functional dyspepsia. Mosapride was as effective as famotidine and itopride, but more effective than tandospirone, in improving overall or individual symptoms of functional dyspepsia in randomized trials. However, in one randomized, double-blind trial in patients with mild to severe disease, the improvement in overall symptoms of functional dyspepsia did not differ significantly between mosapride or placebo treatment. Mosapride was well tolerated, with diarrhoea/loose stools, dry mouth, malaise and headache being reported in <5% of patients.     

Review article: rabeprazole's tolerability profile in clinical trials

Rabeprazole is a new member of a class of substituted benzimidazole drugs known as proton pump inhibitors. Comparative trials have demonstrated that it is at least as effective as omeprazole for the treatment of gastro-oesophageal reflux disease (GERD), duodenal ulcers, or gastric ulcers. It is significantly more effective than histamine₂-receptor antagonists for acid suppression, GERD healing and pain relief, and duodenal ulcer healing and pain relief. Adverse events reported during clinical trials provide an important indication of a medication's tolerability. We demonstrate that rabeprazole has a favourable adverse events profile. It is well tolerated in placebo-controlled studies and comparative trials with omeprazole and H₂-receptor antagonists. Moreover, no dose adjustments are required for special populations, such as the elderly or patients with renal or mild-to-moderate hepatic disease. Adverse events data from clinical trials support the use of rabeprazole as a treatment for acid-related diseases.     

Evaluation and significance of reflux from the duodenum and stomach

Duodeno-gastric and gastro-oesophageal reflux are of potential significance in the pathogenesis of dyspepsia and heartburn. However, convincing evidence that duodeno-gastric reflux, in itself, causes symptoms is not yet available, and none of the techniques designed to measure duodeno-gastric reflux has gained broad clinical acceptance. Monitoring of oesophageal pH has become the gold standard, however, for demonstrating gastro-oesophageal reflux disease, and the technique has become fairly standardized. The importance of measuring gastro-oesophageal reflux is not so much to differentiate normal (physiological) reflux from abnormal (pathological) reflux, but rather to assess the effect of treatment and to quantify the relationship between gastro-oesophageal reflux and symptoms. To achieve the latter, a number of indices have been described and tested, with which the temporal association between reflux and symptoms can be expressed quantitatively. It has become clear that troublesome symptoms may be induced by reflux in the absence of oesophagitis and even pathological oesophageal acid exposure. Primary indications for oesophageal pH monitoring are: reflux symptoms in the absence of oesophagitis, atypical symptoms (with or without oesophagitis), non-cardiac chest pain, and an unsatisfactory response to the treatment of gastro-oesophageal reflux disease.     

Review article: the pharmacokinetics of rabeprazole in health and disease

Rabeprazole, a newly developed proton pump inhibitor, has been shown to be effective for the treatment of gastric and duodenal ulcers and for gastro-oesophageal reflux disease. It is a rapid and potent inhibitor of gastric H⁺,K⁺-ATPase, the gastric acid (proton) pump. The maximum plasma concentration ( C _max) and the area under the plasma concentration time curve ( AUC ) are linearly related to dose, while the time to maximum plasma concentration ( t _max) and elimination half-life ( t _½) are dose-independent. Rabeprazole is extensively metabolized in the liver via the cytochrome P450 enzyme system, and its metabolites are excreted primarily in the urine. Rabeprazole does not accumulate with repeated dosing. Its bioavailability is not influenced by the coingestion of either food or antacids. The pharmacokinetic profile of rabeprazole is substantially altered in the elderly and patients with stable compensated chronic cirrhosis; however, these alterations are not associated with clinically significant abnormalities in laboratory parameters or serious adverse events. The influence of severe decompensated liver disease on the pharmacokinetics of rabeprazole has not been assessed. The pharmacokinetic profile of rabeprazole is not significantly altered by renal dysfunction requiring maintenance haemodialysis. These findings suggest that dosage adjustment is not required in these special patient populations. Caution should be exercised, however, in patients with severe liver disease.     

Current concepts in clinical therapeutics: peptic ulcer disease

The epidemiology, pathophysiology, diagnosis, clinical presentation, and treatment of peptic ulcer disease (PUD) are reviewed. PUD occurs commonly, with about 4 million Americans affected in a year. Cigarette smoking, aspirin use, and prolonged corticosteroid use are associated with PUD. The disease's etiology is multifactorial; the long-held assumption that ulcers develop solely because of increased gastric acid secretion is no longer valid. Although duodenal ulcer patients are frequently hypersecretors of acid, gastric ulcer patients more commonly have defective mechanisms for protecting the mucosal lining from acid, pepsin, and other agents. PUD is best diagnosed using an upper gastrointestinal roentgenographic series or using endoscopy. The clinical presentations, which involve epigastric abdominal pain that is relieved by food, milk, or antacids, may aid in diagnosis but are not usually definitive. Treatment is designed to relieve symptoms, heal the ulcer, prevent recurrences, and prevent complications. Of the four currently available drug treatments (cimetidine, ranitidine, antacids, and sucralfate), the treatment of first choice is cimetidine or ranitidine for four or six weeks, respectively, for duodenal and gastric ulcer patients. Antacids should be used as needed for pain, and the patient should be reassessed at the end of this period. For most patients, neither cimetidine nor ranitidine is demonstrably superior to one another. Several agents are under investigation in the U.S., including other H2-receptor antagonists (famotidine and nizatidine), proton-pump inhibitors (omeprazole), prostaglandins (misoprostol, arbasprostil, enprostil, and trimoprostil), antimuscarinic agents (pirenzepine), and tricyclic antidepressants (doxepin and trimipramine). peptic ulcer disease is an important disease. It is best treated with H2-receptor antagonists supplemented with antacids as needed for pain.     

Review article: the treatment of Helicobacter pylori infection

The discovery of Helicobacter pylori has stimulated great interest in its role in gastritis, non-ulcer dyspepsia and peptic ulceration. Treatment regimens to eradicate this organism from gastric mucosa have also received considerable attention. Current recommendations limit the use of triple drug combinations only to specific patient groups.     

促胃肠动力药的进展与临床评价

目的：了解胃肠道促动力剂的最新动态。方法：查阅国内外文献,结合基础研究成果对各种药物在治疗消化不良中的地位和疗效进行讨论。结果及结论：胃肠促动力药具有疗效好、不良反应少等特点,除用于消化不良外,尚可治疗食管反流性疾病、慢性胃炎、便秘等,在胃肠疾病的治疗中显示出良好的前景。     

Review article: drug therapy for reflux oesophagitis

Gastro-oesophageal reflux disease is a common disorder and symptoms can be mild to severe. Management of the disease should be individualized. Life-style changes are important for all patients. Drug therapy is often necessary but only very few patients with severe disease need surgical treatment. The purpose of this article is to focus on drug therapy and to review the clinical trials of all the drugs used for gastro-oesophageal reflux disease. Thereafter, judged solely on the data derived from these trials, a practical approach to the management of gastro-oesophageal reflux disease is suggested.     

GM-611 (Chugai Pharmaceutical)

GM-611 is an erythromycin derivative that acts as an agonist at the motilin receptor. It is being developed by Chugai as a potential treatment for gastric motility disorder [169036], as well as reflux esophagitis, non-ulcer dyspepsia and diabetic gastroparesis [347963]. GM-611 is in phase II trials in the US for reflux esophagitis [322624], [347955], [399349]. GM-611 acts by a novel mechanism whereby it stimulates and promotes peristalsis in the stomach and other segments of the gastrointestinal tract [334994]. The drug was shown to produce a dose-dependent sustained depolarization of rabbit duodenal smooth muscle. Depolarization appeared to be associated with activation of monovalent cation-selective channels [273336]. In December 2000, Credit Suisse First Boston predicted that successful development of GM-611 could lead to sales over $500 million [400228].