Lansoprazole: pharmacokinetics,pharmacodynamics and clinical uses

Lansoprazole (Prevacid?, TAP Pharmaceuticals, Inc.) is a substituted benzimidazole that inhibits gastric acid secretion. This agent is approved for the short-term treatment of erosive reflux oesophagitis, active gastric ulcer, active duodenal ulcer and the treatment of non-steroidal anti-inflammatory drug (NSAID)-induced gastric and duodenal ulcers. It is also approved for the long-term treatment of healed reflux oesophagitis, healed duodenal ulcer, the treatment of hypersecretory conditions such as Zollinger-Ellison syndrome and the eradication of Helicobacter pylori as a component of triple therapy with lansoprazole, clarithromycin and amoxicillin, or dual therapy with lansoprazole and amoxicillin. Its mechanism of action is to selectively inhibit the membrane enzyme H⁺/K⁺ATPase in gastric parietal cells. In clinical trials, lansoprazole is more effective than placebo or histamine (H₂)-receptor antagonists in the treatment of reflux oesophagitis. Lansoprazole administered at a dose of 30 mg daily produced faster relief of symptoms and superior healing rates in patients with gastric or duodenal ulcers or reflux oesophagitis than H₂-receptor antagonists. A daily dose of 30 mg lansoprazole reduced epigastric pain faster than omeprazole 20 mg daily in patients with peptic ulcer disease but healing rates at 4 and 8 weeks were similar with both agents at these dosages. Lansoprazole was more effective than H₂-receptor antagonists in patients with Zollinger-Ellison syndrome and produced similar treatment outcome to omeprazole. Lansoprazole in combination with clarithromycin and amoxicillin produced similar rates of eradication of H. pylori. In clinical trials, lansoprazole is well-tolerated and has a low frequency of side effects similar to that of H₂-receptor antagonists or omeprazole.     

The rationale of acid suppression in the treatment of acid-related disease.

Acid-related disorders such as gastric and duodenal ulcers and gastro- oesophageal reflux disease have a high prevalence. Traditionally, acid suppression has proved to be the most effective means by which to heal these disorders, but relapse rates are high after cessation of treatment. Recently, Helicobacter pylori infection has been shown to modify several aspects of gastric function. Eradication of H. pylori infection virtually abolishes duodenal ulcer recurrence, implicating this organism in the pathogenesis of peptic ulcers and initiating a whole new strategy in the management of these acid-related disorders. More potent degrees of acid suppression result in faster healing. Moderate acid suppression, as occurs with H2-receptor antagonists, can heal just as many ulcers if treatment is continued for longer. The combination of proton pump inhibitors and antibiotics have successfully eradicated H. pylori in duodenal ulcer patients. Both H2-receptor antagonists and the proton pump inhibitors have satisfactory safety profiles. Due to their superiority in symptom relief, and in the healing of duodenal and gastric ulcers and erosive oesophagitis, and due to their ability to eradicate H. pylori infection in combination with antibiotics, the proton pump inhibitors will probably become accepted as first-line therapy for the treatment of acid-related diseases.     

Lansoprazole: pharmacokinetics, pharmacodynamics and clinical uses

Lansoprazole (Prevacid, TAP Pharmaceuticals, Inc.) is a substituted benzimidazole that inhibits gastric acid secretion. This agent is approved for the short-term treatment of erosive reflux oesophagitis, active gastric ulcer, active duodenal ulcer and the treatment of non-steroidal anti-inflammatory drug (NSAID)-induced gastric and duodenal ulcers. It is also approved for the long-term treatment of healed reflux oesophagitis, healed duodenal ulcer, the treatment of hypersecretory conditions such as Zollinger-Ellison syndrome and the eradication of Helicobacter pylori as a component of triple therapy with lansoprazole, clarithromycin and amoxicillin, or dual therapy with lansoprazole and amoxicillin. Its mechanism of action is to selectively inhibit the membrane enzyme H+/K+ ATPase in gastric parietal cells. In clinical trials, lansoprazole is more effective than placebo or histamine (H2)-receptor antagonists in the treatment of reflux oesophagitis. Lansoprazole administered at a dose of 30 mg daily produced faster relief of symptoms and superior healing rates in patients with gastric or duodenal ulcers or reflux oesophagitis than H2-receptor antagonists. A daily dose of 30 mg lansoprazole reduced epigastric pain faster than omeprazole 20 mg daily in patients with peptic ulcer disease but healing rates at 4 and 8 weeks were similar with both agents at these dosages. Lansoprazole was more effective than H2-receptor antagonists in patients with Zollinger-Ellison syndrome and produced similar treatment outcome to omeprazole. Lansoprazole in combination with clarithromycin and amoxicillin produced similar rates of eradication of H. pylori. In clinical trials, lansoprazole is well-tolerated and has a low frequency of side effects similar to that of H2-receptor antagonists or omeprazole.     

Lansoprazole. A review of its pharmacodynamic and pharmacokinetic properties and its therapeutic efficacy in acid-related disorders.

Lansoprazole is an effective acid pump inhibitor acting at the final enzymatic step of the acid secretory pathway of the parietal cell, decreasing gastric acid secretion regardless of the primary stimulus. Results of short term (less than 8 weeks) clinical trials have shown lansoprazole to be significantly superior to placebo and ranitidine in the treatment of duodenal ulcer, both in the rate of healing and in overall healing at 4 weeks. Lansoprazole appears to heal duodenal ulcer more quickly than famotidine, and demonstrates slightly greater efficacy at 4 weeks, although both drugs appear to have equivalent efficacy overall. Gastric ulcers and reflux oesophagitis are also healed by lansoprazole 30 mg/day for 4 to 8 weeks, with healing rates after 8 weeks of approximately 85 to 95% for both indications. Lansoprazole appears to be superior to ranitidine and comparable to omeprazole in treating reflux oesophagitis. Furthermore, lansoprazole has relieved reflux symptoms more quickly than either ranitidine or omeprazole. Preliminary data also indicate that lansoprazole may be effective in the treatment of peptic ulcer disease and reflux oesophagitis refractory to H2-receptor antagonists, and in patients with Zollinger-Ellison syndrome. While direct comparisons with omeprazole are limited, results suggest that lansoprazole, used for short term treatment, is at least as effective as omeprazole in the treatment of peptic ulcer and reflux oesphagitis. Lansoprazole has been well tolerated in short term clinical trials, with an incidence of adverse effects comparable with that of other agents in its therapeutic class. Trials assessing long term tolerability data are ongoing and will be required as part of the assessment of the safety profile, if lansoprazole is to be used prophylactically to prevent ulcer recurrence. Thus, by virtue of its ability to heal ulcers and rapidly relieve associated symptomatology, lansoprazole represents a useful alternative for the treatment of acid related disorders.     

Lansoprazole: A Comprehensive Review

Lansoprazole is the second member of the substituted benzimidazole class of antisecretory agents approved for use in the United States. These drugs decrease parietal cell acid secretion by inhibiting H⁺,K⁺-adenosine triphosphatase, the final step in the secretion of acid. Lansoprazole has been studied extensively for the short-term treatment of duodenal and gastric ulcers, reflux esophagitis, and Helicobacter pylori-positive peptic ulcer disease; long-term treatment of Zollinger-Ellison syndrome; and maintenance treatment of erosive esophagitis. A dosage of 30 mg/day produced higher healing rates and equivalent or faster relief of ulcer symptoms than ranitidine or famotidine in patients with duodenal or gastric ulcers and reflux esophagitis. Compared with omeprazole 20 mg/day, that dosage provided faster epigastric pain relief in these patients after 1 week, although healing rates for the two agents were equivalent at 4 and 8 weeks. In patients with peptic ulcer refractory to 8-week therapy with histamine₂-receptor antagonists, healing rates were not significantly different between lansoprazole and omeprazole. In patients with Zollinger-Ellison syndrome, lansoprazole was superior to histamine₂-receptor antagonists and was similar in efficacy, safety, and duration of action to omeprazole. Combinations of lansoprazole or omeprazole with one or two antibiotics produced equivalent eradication of H. pylori. In clinical trials, lansoprazole was well tolerated, with frequency of adverse effects similar to that reported with ranitidine, famotidine, and omeprazole.     

Roxatidine acetate. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic potential in peptic ulcer disease and related disorders.

Roxatidine acetate is a histamine H2-receptor antagonist which, after almost complete oral absorption (greater than 95%), is rapidly converted to its active metabolite, roxatidine, by esterases in the small intestine, plasma and liver. Roxatidine is a potent inhibitor of basal and stimulated gastric acid secretion in animals and humans and, like most other H2-receptor antagonists, has no anti-androgenic effects and does not interfere with the hepatic metabolism of other drugs. Large-scale trials have shown that roxatidine acetate 150mg per day is as effective as standard doses of cimetidine and ranitidine in the treatment of patients with duodenal or gastric ulcer, and that roxatidine acetate 75mg in the evening is likely to become a 'standard' regimen for the prevention of peptic ulcer recurrence. Preliminary data also suggest that roxatidine acetate may be useful in the treatment of reflux oesophagitis and stomal ulcer, and in the prevention of pulmonary acid aspiration. Roxatidine acetate is an H2-receptor antagonist which has been well tolerated in clinical trials. However, broader experience is required before definitive statements about tolerability relative to other H2-receptor antagonists can be made, and before the role of roxatidine acetate in the treatment of reflux oesophagitis and stomal ulcer, and the prophylaxis of acid aspiration pneumonitis, can be clearly defined.     

Identification,Diagnosis, and Treatment of Acid-Related Diseases in the Elderly: Implications for Long-Term Care

Acid-related disorders such as peptic ulcer disease and gastroesophageal reflux disease occur frequently in the elderly and are associated with a high frequency of morbidity and mortality. The proton pump inhibitors lansoprazole and omeprazole produce faster rates of healing and greater symptomatic relief in patients with acid-related disorders than histamine₂-receptor antagonists, are well tolerated, and are associated with few adverse events. Compared with omeprazole, which interacts with diazepam, warfarin, and phenytoin, lansoprazole produces only a minor increase in theophylline clearance. Proton pump inhibitors in combination with antibiotic therapy can eradicate Helicobacter pylori, the main risk factor in the recurrence of peptic ulcer disease, obviating the need for maintenance therapy. Long-term acid suppression with proton pump inhibitors may be necessary to prevent the recurrence of gastroesophageal reflux disease. The safety and efficacy profile of these agents makes them ideal for the treatment of acid-related diseases in elderly patients. (Pharmacotherapy 1997;17(5);938–958)     

Omeprazole. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in peptic ulcer disease and Zollinger-Ellison syndrome

Omeprazole is a substituted benzimidazole derivative which markedly inhibits basal and stimulated gastric acid secretion. It has a unique mode of action, irreversibly blocking the so-called proton pump of the parietal cell which is supposedly the terminal step in the acid secretory pathway. In animals, on a weight basis, omeprazole is 2 to 10 times more potent than cimetidine in inhibiting gastric acid secretion. Toxicological studies in rats have shown that very high doses of omeprazole administered for 2 years produce hyperplasia of gastric enterochromaffin-like cells and carcinoids, a few with proliferations into the submucosa. The significance of such findings to the clinical situation is wholly speculative and requires further research. Preliminary studies in patients with duodenal ulcers or Zollinger-Ellison syndrome have found no mucosal changes which would suggest that the drug represents a risk for development of carcinoid tumours at therapeutic dosages. In patients with duodenal ulcers omeprazole, at dosages of at least 20mg once daily, produced ulcer healing rates of between 60 and 100% after 2 weeks and between 90 and 100% after 4 weeks, even in patients resistant to treatment with H2-receptor antagonists. Comparative trials clearly demonstrated that omeprazole 20 to 40 mg administered once daily was significantly more effective than usual dosage regimens of cimetidine and ranitidine in healing duodenal ulcers during 2 to 4 weeks of treatment. At present no data are available evaluating omeprazole as maintenance therapy once ulcers have healed. Other clinical trials have also shown that omeprazole is effective for treating gastric ulcers, ulcerative peptic oesophagitis, and Zollinger-Ellison syndrome. In patients with Zollinger-Ellison syndrome the profound and long lasting antisecretory activity of omeprazole may make it the drug of choice for treating the massive acid hypersecretion associated with the disease, especially when H2-receptor antagonists are ineffective. During clinical trials reported to date omeprazole has been very well tolerated but further clinical experience is essential to fully evaluate its safety profile. Thus, omeprazole represents a pharmacologically unique antisecretory drug which is very effective for rapidly healing peptic ulcers and peptic oesophagitis, and for reducing gastric acid hypersecretion in patients with Zollinger-Ellison syndrome. If the apparent absence of undesirable mucosal morphological changes during treatment with usual doses in patients with peptic ulcer disease is confirmed, it may be a major advance in the treatment of these diseases.     

Optimising acid inhibition treatment

Acid inhibition is safe and useful in several clinical settings. Proton pump inhibitors are more effective than H2-receptor antagonists in virtually all cases. Proton pump inhibitors should be used in: the eradication of Helicobacter pylori; the treatment of non-H. pylori-related peptic ulcer healing; for the prevention and treatment of non-steroidal anti-inflammatory drug-induced upper digestive lesions; for bleeding peptic lesions; and, especially, in the short-term and long-term control of gastro-oesophageal reflux disease. The timing, the dosing and the specific drugs should be adapted to the particular patient, clinical situation and local factors. For instance, in a patient with active bleeding from a duodenal ulcer, intravenous constant infusion should be the preferred treatment. When seeking oral 'potent' acid inhibition (refractory gastro-oesophageal reflux disease, and perhaps Barrett's oesophagus), available data suggest that the pharmacological and clinical profiles of esomeprazole are slightly better.     

Treatment of peptic ulcer disease in the arthritic patient

Dyspepsia associated with arthritis and non-steroidal anti-inflammatory drugs (NSAIDs) is a common clinical problem. Up to 80% of deaths attributable to peptic ulceration may be associated with NSAID usage. The problem is foremost in the elderly population, in which there has been an increase both in the incidence of peptic ulcers and in the use of NSAIDs. Although the development of duodenal ulceration is not clearly associated with NSAIDs, it is accepted that these drugs increase the risk of gastric ulceration and the occurrence of peptic ulcer complications. Asymptomatic peptic ulceration is common, and patients taking NSAIDs are often asymptomatic prior to presentation with life-threatening complications. The key principle in management of this problem is prevention through careful selection of patients for NSAID use, adequate treatment of peptic ulceration and maintenance of remission. A variety of effective drugs are available for the treatment of peptic ulcers, including H2-receptor antagonists, pirenzepine, sucralfate and colloidal bismuth subcitrate. However, it is recognised that peptic ulceration is a chronic disease with a relapsing-remitting course, often with asymptomatic ulcer episodes. The knowledge that current ulcer-healing strategies do not significantly alter this natural history has lead to increasing efforts to prevent relapse with effective 'maintenance' therapy.     

Omeprazole. An updated review of its pharmacology and therapeutic use in acid-related disorders.

Omeprazole is the first of a new class of drugs, the acid pump inhibitors, which control gastric acid secretion at the final stage of the acid secretory pathway and thus reduce basal and stimulated acid secretion irrespective of the stimulus. In patients with duodenal or gastric ulcers, omeprazole as a single 20 mg daily dose provides more rapid and complete healing compared with ranitidine 150 mg twice daily or 300 mg at nighttime, or cimetidine 800 or 1000 mg/day. Patients poorly responsive to treatment with histamine H2-receptor antagonists respond well to omeprazole--most ulcers healed within 4 to 8 weeks of omeprazole 40 mg/day therapy. Omeprazole 20 or 40 mg/day has been administered as maintenance therapy for peptic ulcer disease for up to 5.5 years with very few ulcer recurrences. In patients with erosive or ulcerative oesophagitis, omeprazole 20 or 40 mg/day produces healing in about 80% of patients after 4 weeks, and is superior to ranitidine with respect to both healing and symptom relief. Healing rates of greater than 80% are achieved after 8 weeks in patients with severe reflux oesophagitis unresponsive to H2-receptor antagonists. Maintenance therapy with a daily 20 mg dose prevents relapse in about 80% of patients over a 12-month period. Omeprazole is considered to be the best pharmacological option for controlling gastric acid secretion in patients with Zollinger-Ellison syndrome. Daily dosages of 20 to 360 (median 60 to 70 mg successfully reduce basal acid output to target levels (less than 10 mmol/h or less than 5 mmol/h in patients with severe oesophagitis or partial gastrectomy) during treatment for up to 4 years. Omeprazole is well tolerated in short term studies (up to 12 weeks); the reported incidence of serious side effects (about 1%) being similar to that seen in patients treated with an histamine H2-receptor antagonist. The longer term tolerability of omeprazole has been investigated in patients treated for up to 5.5 years. Slight hyperplasia, but no evidence of enterochromaffin-like (ECL) cell dysplasia or neoplasia or ECL cell carcinoids has been reported. ECL cell carcinoids have been observed in rats after life-long treatment with high doses of omeprazole or ranitidine, or in rats with partial corpectomy; the weight of experimental evidence indicates that this is a result of prolonged hypergastrinaemia.(ABSTRACT TRUNCATED AT 400 WORDS)     

Peptic Ulcer Disease: An Update

Peptic ulcers can develop when there is an imbalance between gastric acid secretion and gastroduodenal mucosal defense. Investigators are looking at the role of Helicobacter pylori in the development of peptic ulcer disease; eradication of the microorganism may reduce recurrence. Approved drug therapy includes H₂-receptor antagonists, omeprazole, sucralfate, and antacids. Recommendations for treating and counseling patients are provided.     

Omeprazole: a pharmacoeconomic evaluation of its use in duodenal ulcer and reflux oesophagitis

Omeprazole regulates gastric acid secretion and is an effective treatment of acute duodenal ulcer and reflux oesophagitis, achieving more rapid healing and symptomatic relief than histamine H 2-receptor antagonists. When administered as maintenance therapy, omeprazole reduces the incidence of relapse. The drug is also highly effective in patients poorly responsive to histamine H 2-receptor antagonists. The daily acquisition cost of omeprazole is higher than that of histamine H 2-receptor antagonists in many countries, and thus it is important to evaluate the pharmacoeconomic impact of omeprazole in the short and long term treatment of duodenal ulcer and reflux oesophagitis. Pharmacoeconomic analyses have been performed in several clinical settings using pooled data from clinical trials or simulated models of clinical practice. In a single analysis using Finnish cost data, omeprazole was more cost effective than ranitidine in the treatment of duodenal ulcer disease over a 6-month period. The cost effectiveness of omeprazole was comparable to that of sucralfate-containing regimens, with patients receiving omeprazole being healed more quickly and experiencing a greater number of healthy days. Using a computer-model simulation and Swedish cost data, omeprazole was more cost effective than ranitidine when administered as intermittent treatment of duodenal ulcer over 5 years. Preliminary reports indicate that regimens which eradicate Helicobacter pylori are more cost effective than those which do not. As short term treatment of reflux oesophagitis, omeprazole 20 to 40 mg/day was the dominating treatment strategy, being less costly and more effective than ranitidine 300 to 1200 mg/day. Omeprazole 20 mg/day produced symptom-free days more cost effectively than either cimetidine 1.6 g/day or ranitidine 300 mg/day. More importantly, as long term (maintenance or intermittent) treatment of reflux oesophagitis, omeprazole 20 mg/day was more cost effective than both ranitidine 150 mg twice daily and 'phase 1' therapy (diet and antacids) over 6 and 12 months. Thus, based on analyses evaluated, omeprazole appears to be more cost effective than ranitidine in the short term treatment of duodenal ulcer. Results for long term treatment are less clear cut, but full details from some studies are not yet available. For the short term treatment of reflux oesophagitis omeprazole is more cost effective than ranitidine or cimetidine and for long term treatment omeprazole is more cost effective than ranitidine. As treatment for reflux oesophagitis, omeprazole is considered to be the dominating treatment strategy.     

Pharmacokinetics and pharmacodynamics of famotidine in patients with reflux oesophagitis

Summary The pharmacokinetics, pharmacodynamic effect and clinical efficacy of famotidine were studied in 10 patients with reflux oesophagitis Grades I and II. For the pharmacokinetic studies the patients received 20 mg famotidine i. v.The half-life of famotidine was 3.8 h, the total plasma clearance was 297 ml·min^–1, and a steady state volume of distribution of 1.21·kg^–1 was found. For pharmacodynamic assessment, intraoesophageal pH-metry was performed without and after acute treatment with famotidine 20 mg i. v. and following 3 weeks of oral famotidine 80 mg b. d. The resultant percentage total acid exposure time (pH<4 within 24 h) were 23.9%, 19.0% and 19.2% (median), respectively (NS). At the end of 6 weeks of oral therapy, symptomatic and endoscopic improvement had occurred in 9 and 5 patients, respectively.Our study shows that the pharmacokinetics of famotidine in patients with reflux oesophagitis is comparable to that in healthy volunteers and peptic ulcer patients. The clinical response to the treatment appeared comparable to that found after other H₂-receptor antagonists.     

Ranitidine. An updated review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in peptic ulcer disease and other allied diseases

Ranitidine, a histamine H2-receptor antagonist, is now well established as a potent inhibitor of gastric acid secretion effective in the treatment and prophylaxis of gastrointestinal lesions aggravated by gastric acid secretion. Therapeutic trials involving several thousands of patients with peptic ulcer disease confirm that ranitidine 300mg daily administered orally in single or divided doses is at least as effective as cimetidine 800 to 1000mg daily in increasing the rate of healing of duodenal and gastric ulcers. Similar dosages of ranitidine have been shown to relieve the symptoms of reflux oesophagitis and heal or prevent gastrointestinal damage caused by ulcerogenic drugs. Ranitidine 150mg orally at night maintains ulcer healing in the long term. Ranitidine has also demonstrated good results in the treatment of Zollinger-Ellison syndrome and in the prevention of aspiration pneumonitis when given prior to surgery and to pregnant women at full term. It may also have a place in the management of acute upper gastrointestinal bleeding and in the prevention of stress ulcers in the intensive care setting, although these areas require further investigation. Ranitidine has been used safely in obstetric patients during labour, in children, the elderly, and in patients with renal impairment when given in appropriate dosages. The drug is very well tolerated and is only infrequently associated with serious adverse reactions or clinically significant drug interactions. Even at high dosages, ranitidine appears devoid of antiandrogenic effects. Ranitidine is clearly comparable or superior to most other antiulcer agents in the treatment and prevention of a variety of gastrointestinal disorders associated with gastric acid secretion. With its favourable efficacy and tolerability profiles, ranitidine must be considered a first-line agent when suppression of gastric acid secretion is indicated.     

Ranitidine: a pharmacoeconomic evaluation of its use in acid-related disorders

Ranitidine is a histamine H 2-receptor antagonist which, on the basis of its well established tolerability and efficacy profile, has been widely prescribed for the treatment of ulcer disease and mild to moderate reflux oesophagitis. However, the advent of more powerful gastric acid inhibitors (e.g. acid pump inhibitors) and the realisation of the role of Helicobactor pylori infection in duodenal ulcer disease could have considerable clinical and economic implications for the use of ranitidine (and other H 2-receptor antagonists). Simulation modelling studies based on current pricing policies in Europe predict that ranitidine-based treatment will be less cost effective than omeprazole in the short term healing of duodenal ulcer and reflux oesophagitis disease. During longer term treatment, omeprazole is expected to be the dominating strategy over ranitidine-based therapy in Europe and the US. However, the inherent limitations of modelling studies reinforce the need for randomised prospective trials, preferably conducted in a general practice setting and including a quality-of-life analysis. Of the currently accepted approaches for the long term management of recurrent duodenal ulcer disease, daily maintenance therapy with ranitidine has been shown to be more cost effective than intermittent treatment for up to 2 years in the US. The annual cost of providing continuous maintenance therapy with ranitidine 150 mg/day is higher than with cimetidine 400 mg/day, although the extra benefits include a reduced risk of pain and discomfort from an expected lower rate of ulcer recurrence with ranitidine. Simultaneous ulcer healing and eradication of H. pylori markedly reduces relapse rates and is likely to become the management strategy of choice in H. pylori-positive patients, particularly with the advent of more convenient, well tolerated and effective regimens. Moreover, widespread clinical acceptance of H. pylori eradication may yield substantial cost savings to society by reducing the overall need for long term antisecretory therapy. Nonetheless, maintenance therapy with histamine H 2-receptor antagonists remains indicated for patients at high risk of ulcer recurrence who are poorly responsive to or cannot tolerate H. pylori eradication regimens. In summary, the proven efficacy and tolerability of ranitidine will ensure its continued use in the treatment of many patients with duodenal ulcer and mild to moderate reflux oesophagitis. However, there is increasing clinical and economic data favouring the selection of omeprazole in patients with more severe symptoms of these diseases.(ABSTRACT TRUNCATED AT 400 WORDS)     

Omeprazole in peptic ulcers resistant to histamine H2-receptor antagonists

Eighteen patients with duodenal, gastric or jejunal ulcers, resistant to at least 3 months treatment with histamine H2-receptor antagonists, singly or in combination with other anti-ulcer drugs, were treated with 40 mg omeprazole once daily for up to 8 weeks. All ulcers healed, the majority within two weeks. After ulcer healing patients were given maintenance therapy with high doses of cimetidine or ranitidine. Of 15 patients on maintenance therapy with H2-receptor antagonists, 12 (80%) developed a relapse after a period ranging from 3 to 52 weeks. Two patients were lost to follow-up. After re-healing on 40 mg omeprazole, two patients were given 20 mg omeprazole daily as maintenance therapy but relapses occurred again after 14 and 26 weeks respectively. After re-healing on 40 mg omeprazole, these two patients and one additional patient received maintenance therapy with 40 mg omeprazole daily. At present these three patients have been relapse-free for periods varying from 16 to 52 weeks. No side effects were registered during treatment with omeprazole. It is therefore concluded that omeprazole is highly effective in healing refractory peptic ulcers and that omeprazole maintenance therapy may be useful for prevention of relapse. Patients are sometimes seen with peptic ulceration which appears resistant to therapy with histamine H2-receptor antagonists, colloidal bismuth subcitrate, sucralfate or pirenzepine, either given as monotherapy for a prolonged period of time or as combination therapy. Usually the reason for such therapeutic failure remains obscure. Whether virtually total abolition of acid secretion will allow ulcer healing in these circumstances is unknown.(ABSTRACT TRUNCATED AT 250 WORDS)     

Histamine H2-receptor antagonists in peptic ulcer disease. Efficacy in healing peptic ulcers.

Duodenal ulcer healing depends on the degree and length of inhibition of gastric secretion and upon the duration of therapy, while gastric ulcer healing is dependent mainly on the duration of therapy. Currently marketed doses of the histamine H2-receptor antagonists heal between 77 and 92% of duodenal ulcers at 4 weeks, and adjuvant treatment to eradicate Helicobacter pylori increases this rate. Once-daily administration is as effective as more frequent dosing regimens and may even result in higher healing rates. Gastric ulcers heal more slowly, but 75 to 88% of ulcers heal after 8 weeks of treatment. While newer more potent acid suppressors such as omeprazole heal ulcers slightly more quickly, the H2-receptor antagonists have an unparalleled safety record of over 15 years. It is unlikely that the prostaglandin analogues can improve on the efficacy of the H2-receptor antagonists with as low an incidence of side effects.