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: 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.     

Famotidine. Pharmacodynamic and pharmacokinetic properties and a preliminary review of its therapeutic use in peptic ulcer disease and Zollinger-Ellison syndrome

Famotidine is a new histamine H2-receptor antagonist. On a weight basis, famotidine is 20 times more potent than cimetidine and 7.5 times more potent than ranitidine in inhibiting basal and pentagastrin-stimulated gastric acid secretion in humans. Therapeutic trials have shown that famotidine 20 mg twice daily or 40 mg at bedtime may be an effective alternative to standard doses of cimetidine for healing gastric ulcers and to standard doses of cimetidine and ranitidine for healing duodenal ulcers. When used prophylactically, a single 20 mg dose of famotidine at night decreases the incidence of duodenal ulcer recurrence (versus placebo). However, further study is needed to clarify the comparative efficacy of the H2-receptor antagonists, in particular as maintenance therapy for healed peptic ulcer. Preliminary results in a few patients with Zollinger-Ellison syndrome indicate that famotidine, alone or in combination with an anticholinergic agent, gives good control of gastric acid hyperacidity with no evidence of biochemical or haematological toxicity. Famotidine appears to be well tolerated. Unlike cimetidine, it does not have antiandrogenic effects or alter hepatic metabolism of drugs. However, wider clinical experience with famotidine is needed to accurately determine its relative tolerability compared with other anti-ulcer drugs. Thus, famotidine appears to be a suitable and well tolerated alternative to cimetidine and ranitidine for healing peptic ulcers, but wider clinical experience is needed to assess its relative efficacy and tolerability in the long term maintenance treatment of patients with healed ulcers as well as in patients with Zollinger-Ellison syndrome.     

Lansoprazole: an update of its place in the management of acid-related disorders

Lansoprazole is an inhibitor of gastric acid secretion and also exhibits antibacterial activity against Helicobacter pylori in vitro. Current therapy for peptic ulcer disease focuses on the eradication of H. pylori infection with maintenance therapy indicated in those patients who are not cured of H. pylori and those with ulcers resistant to healing. Lansoprazole 30 mg combined with amoxicillin 1g, clarithromycin 250 or 500mg, or metronidazole 400 mg twice daily was associated with eradication rates ranging from 71 to 94%, and ulcer healing rates were generally >80% in well designed studies. In addition, it was as effective as omeprazole- or rabeprazole-based regimens which included these antimicrobial agents. Maintenance therapy with lansoprazole 30 mg/day was significantly more effective than either placebo or ranitidine in preventing ulcer relapse. Importantly, preliminary data suggest that lansoprazole-based eradication therapy is effective in children and the elderly. In the short-term treatment of patients with gastro-oesophageal reflux disease (GORD), lansoprazole 15, 30 or 60 mg/day was significantly more effective than placebo, ranitidine 300 mg/day or cisapride 40 mg/day and similar in efficacy to pantoprazole 40 mg/day in terms of healing of oesophagitis. Lansoprazole 30 mg/day, omeprazole 20 mg/day and pantoprazole 40 mg/day all provided similar symptom relief in these patients. In patients with healed oesophagitis. 12-month maintenance therapy with lansoprazole 15 or 30 mg/day prevented recurrence and was similar to or more effective than omeprazole 10 or 20 mg/day. Available data in patients with NSAID-related disorders or acid-related dyspepsia suggest that lansoprazole is effective in these patients in terms of the prevention of NSAID-related gastrointestinal complications, ulcer healing and symptom relief. Meta-analytic data and postmarketing surveillance in >30,000 patients indicate that lansoprazole is well tolerated both as monotherapy and in combination with antimicrobial agents. After lansoprazole monotherapy commonly reported adverse events included dose-dependent diarrhoea, nausea/vomiting, headache and abdominal pain. After short-term treatment in patients with peptic ulcer, GORD, dyspepsia and gastritis the incidence of adverse events associated with lansoprazole was generally < or = 5%. Similar adverse events were seen in long-term trials, although the incidence was generally higher (< or = 10%). When lansoprazole was administered in combination with amoxicillin, clarithromycin or metronidazole adverse events included diarrhoea, headache and taste disturbance. In conclusion, lansoprazole-based triple therapy is an effective treatment option for the eradication of H. pylori infection in patients with peptic ulcer disease. Preliminary data suggest it may have an important role in the management of this infection in children and the elderly. In the short-term management of GORD, lansoprazole monotherapy offers a more effective alternative to histamine H2-receptor antagonists and initial data indicate that it is an effective short-term treatment option in children and adolescents. In adults lansoprazole maintenance therapy is also an established treatment option for the long-term management of this chronic disease. Lansoprazole has a role in the treatment and prevention of NSAID-related ulcers and the treatment of acid-related dyspepsia; however, further studies are needed to confirm its place in these indications. Lansoprazole has emerged as a useful and well tolerated treatment option in the management of acid-related disorders.     

Dose-related healing of duodenal ulcer with the proton pump inhibitor lansoprazole

Lansoprazole (AG 1749) is a novel substituted benzimidazole which inhibits gastric acid secretion by blocking H+,K(+)-ATPase. This randomized, double-blind multicentre trial studied the dose-response relationship of lansoprazole on ulcer healing and compared it with ranitidine in 314 out-patients with endoscopically assessed, symptomatic duodenal ulcer. Cumulative healing rates with Lansoprazole 7.5, 15, and 30 mg o.m. were 48, 59, and 74% at 2 weeks and 75, 84, and 95% at 4 weeks, respectively (intention-to-treat); the difference of the healing rates between 7.5 and 30 mg groups was significant (P less than 0.001). Corresponding healing rates for 300 mg ranitidine nocte were 51 and 89%. Pain relief was similar in all treatment groups. Lansoprazole was well tolerated. During a follow-up of 6 months relapse rates after lansoprazole 7.5, 15, and 30 mg were 21, 29, and 22%, respectively; the relapse rate after ranitidine 300 mg was 20%. In conclusion, lansoprazole provides faster healing of duodenal ulcer than ranitidine and a similar relapse pattern. For further trials in peptic ulcer disease a daily dose of lansoprazole 30 mg o.m. is recommended.     

Rapid healing of gastric ulcers with lansoprazole

Background: Lansoprazole is a new proton pump inhibitor which powerfully decreases acid secretion. Methods: We compared the efficacy and short-term safety of lansoprazole against ranitidine in the healing of gastric ulcer. This was a parallel group, comparative multicentre, prospectively randomized, double-blind study which included 250 patients with gastric ulcer, 219 of whom had follow-up endoscopic data. Results: Both lansoprazole 30 mg and 60 mg daily produced significantly more rapid healing of gastric ulcer than ranitidine 300 mg nightly with healing rates after 4 weeks of 78% (P < 0.05), 84% (P < 0.01) and 61%, respectively. After 8 weeks, the corresponding healing rates were 99%, 97% and 91% (P = 0.08). Symptom relief was similar for all treatment groups, but fewer antacids were used by patients receiving lansoprazole. Sixty-nine patients experienced 91 adverse events; the incidence, pattern and severity was similar across all three treatment groups. Conclusions: Lansoprazole 30 mg and 60 mg once daily had similar efficacy. Both were superior to ranitidine 300 mg nocte in healing gastric ulcer. The short-term safety profile of lansoprazole was similar to ranitidine. These data indicate that lansoprazole should be used at a dose of 30 mg once daily for the treatment of gastric ulcers.     

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 versus famotidine in the healing and relapse of duodenal ulcer

Sixty patients with symptomatic duodenal ulcer were randomized to receive either omeprazole (20 mg each morning) or famotidine (40 mg at night time) for 2–4 weeks in a double-blind parallel group clinical trial. Healing rates were higher with omeprazole in comparison with famotidine after 2 weeks (77%vs. 40%, P < 0.001) and 4 weeks (93%vs. 80%, P= 0.2) of treatment. Assessment of daily diary cards completed by all patients revealed that omeprazole rapidly relieved ulcer-related day pain and nocturnal pain in comparison to famotidine. Treatment with omeprazole for 2 weeks was also associated with lower cumulative antacid intake (P < 0.05) and reduced absenteeism from work. Helicobacter pylori infection was present in all patients and remained unaffected by treatment with either of the drugs. None of the drugs produced any significant adverse effects. During 6 months follow-up of all the patients after ulcer healing (without maintenance therapy), ulcer relapse was seen in 40% of omeprazole- and 37% of famotidine-treated patients (P > 0.1). The duration of ulcer-free period following initial healing of ulcer was also similar in both the groups (median time: 22 weeks for omeprazole, 21 weeks for famotidine). We conclude that omeprazole is superior to famotidine in rapidly healing duodenal ulcers and achieving more rapid pain relief, but does not influence subsequent ulcer relapse.     

Proton Pump Inhibitors and Acid-Related Diseases

Proton pump inhibitors (PPIs) are targeted to the gastric acid pump, H⁺,K⁺-adenosine triphosphatase (ATPase). The drugs accumulate in the acid space of the parietal cell and convert to active sulfenamide by an acid-catalyzed reaction. Consequent covalent inhibition of H⁺,K⁺-ATPase blocks the final step of acid secretion, hence the PPIs omeprazole, lansoprazole, and pantoprazole are more effective than histamine₂-receptor antagonists (H₂RAs) in controlling acid secretion. Preclinical short- and long-term clinical surveillance data show these drugs to be well tolerated and safe. The PPIs heal the lesions of gastroesophageal reflux disease and lessen symptoms more effectively and more quickly than the H₂RAs, and are effective' and faster acting for peptic ulcer disease. Helicobacter pylori is causally implicated in the majority of peptic ulcers and in atrophic gastritis. Since PPIs, but not H₂RAs, are synergistic with antibiotics in eradicating H. pylori, their use is appropriate in all acid-related diseases since all patients who are H. pylori positive require eradication as well as healing.     

Lansoprazole is superior to ranitidine as maintenance treatment for the prevention of duodenal ulcer relapse

AIM: To compare lansoprazole 30 mg once daily, lansoprazole 15 mg once daily and ranitidine 150 mg once nightly in the prevention of duodenal ulcer relapse in patients whose duodenal ulcers had been previously healed with lansoprazole 30 mg once daily or ranitidine 300 mg nightly. METHODS: A double-blind, parallel group, randomized multicentre study conducted in 33 centres in the UK, Eire, Sweden and Australia. Two hundred and nineteen patients with a duodenal ulcer were randomized to receive lansoprazole 30 mg and 217 to receive ranitidine 300 mg for 8 weeks. Patients were then re-randomized to receive lansoprazole 30 mg (122 patients), lansoprazole 15 mg (121 patients) or ranitidine 150 mg (116 patients) for 12 months. All patients had an endoscopically-proven duodenal ulcer at baseline and were considered suitable for long-term maintenance therapy to prevent relapse. RESULTS: Significantly more patients were healed on lansoprazole (98%) compared to ranitidine (89%) (P < 0.001, Fisher's exact test). Lansoprazole provided more rapid symptom relief than ranitidine. Lansoprazole 30 mg and lansoprazole 15 mg increased the probability of not relapsing in comparison to ranitidine (P = 0.001 and 0.06, respectively, life-table analysis). Relapse rates over the 12 months were lower in the lansoprazole treatment groups (lansoprazole 30 mg, 5%; lansoprazole 15 mg, 12%; and ranitidine, 21%; lansoprazole 30 mg vs. ranitidine 150 mg, P = 0.002). Symptoms were well controlled in both groups during the maintenance phase. All treatments were well tolerated with no major differences seen in adverse event profiles between treatment groups. CONCLUSIONS: Both doses of lansoprazole (30 mg and 15 mg) were superior to ranitidine 150 mg in the prevention of duodenal ulcer relapse. Lansoprazole was superior to ranitidine in terms of symptom control and duodenal ulcer healing. Both treatments were well tolerated.     

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.     

Comparison of famotidine with cimetidine and ranitidine

The pharmacodynamic, therapeutic, and toxicologic properties of famotidine are evaluated and compared with those of cimetidine and ranitidine. Famotidine, an H2-receptor antagonist with a thiazole nucleus, is approximately 7.5 times more potent than ranitidine and 20 times more potent than cimetidine on an equimolar basis. Therapeutic trials indicate that famotidine 20 mg b.i.d. or 40 mg at bedtime is as effective as standard doses of cimetidine and ranitidine for healing duodenal ulcers. A dose of 40 mg at bedtime appears to heal benign gastric ulcers. A single nocturnal dose of 20 mg is effective in preventing duodenal ulcer relapse. Further studies are required that compare the efficacy of famotidine with cimetidine and ranitidine in the treatment of gastric ulcers and in the prevention of recurrent duodenal ulcers. The overall incidence of adverse effects observed with famotidine appears to be similar to that reported for cimetidine and ranitidine. Like ranitidine, famotidine does not have antiandrogenic effects or substantially inhibit the hepatic metabolism of drugs. Because of its increased antisecretory potency and lack of antiandrogenic effects at higher doses, famotidine may be the H2-receptor antagonist of choice in treating Zollinger-Ellison syndrome. Additional clinical experience, as well as cost and safety factors, will determine the place of famotidine in treating and preventing acid-peptic disorders.     

Comparison of omeprazole and lansoprazole in short-term triple therapy for Helicobacter pylori infection

Background:

Effective anti-Helicobacter pylori therapies with few side-effects are needed.

Aim:

To study the effectiveness of short-term triple therapy with amoxycillin, clarithromycin and either omeprazole or lansoprazole for eradication and healing of peptic ulcers.

Methods:

Patients with gastric or duodenal ulcers received amoxycillin (1 g b.d.), clarithromycin (500 mg b.d.) and lansoprazole (30 mg b.d.) (LAC) or omeprazole (20 mg b.d.) (OAC) for 7 days. Endoscopic examinations were performed before treatment and at least 4 weeks after completion of therapy. H. pylori status was confirmed by rapid urease test and histological examination (Giemsa stain) from gastric biopsies taken from both the antrum and the body.

Results:

A total of 356 patients were randomized in this single-blind study. On a per protocol basis, H. pylori was eradicated in 134 of 170 patients (79%) in the lansoprazole group and in 105 of 146 (72%) in the omeprazole group (P = 0.189); and in intention-to-treat analysis 72% and 62%, respectively (P = 0.043). Healing of the ulcers was obtained in 166 of 186 (98%), and in 139 of 146 patients (95%), respectively (P = 0.357). Side-effects occurred in two patients in the LAC group and in six in the OAC group B (four stopped therapy).

Conclusions:

This study has shown that the two regimens are highly effective in healing duodenal ulcers and are well tolerated. Neither treatment achieves the ideal cure rate for H. pylori. Lansoprazole does not appear to have a significant advantage over omeprazole either in ulcer healing or in H. pylori eradication.

     

消化性溃疡的病因和药物治疗

消化性溃疡是我国人群中常见病之一 ,各种因素如幽门螺杆菌感染、药物、遗传及社会心理因素等均可诱发或促进本病的发生。组胺H2 受体拮抗剂如法莫替丁、尼扎替丁等和质子泵抑制剂如奥美拉唑、兰索拉唑等抗酸分泌药物与胃粘膜保护剂如硫糖铝混悬液、胶态次枸椽酸铋等联合应用可有效的治疗消化性溃疡病。应用奥美拉唑、阿莫西林及克拉霉素三联 7d治疗可有效的根治幽门螺杆菌和促进溃疡愈合     

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

Famotidine is a highly selective histamine H2-receptor antagonist. In healthy volunteers and patients with acid hypersecretory disease it is approximately 20 to 50 times more potent at inhibiting gastric acid secretion than cimetidine and 8 times more potent than ranitidine on a weight basis. As shown in placebo-controlled trials, famotidine is effective in healing both duodenal and gastric ulcers. Famotidine 20mg twice daily or 40mg at bedtime achieves healing rates and symptom relief similar or superior to those achieved by cimetidine 800mg daily or ranitidine 300mg daily in patients with peptic ulcer disease. Results of 1 placebo-controlled study suggest that famotidine prevents recurrence of duodenal ulcer, but comparative trials are needed to establish its relative efficacy in maintenance therapy. The few non-comparative trials conducted to date also suggest that famotidine 10 to 20mg twice daily may be effective in the treatment of gastritis and reflux gastro-oesophagitis. In comparative trials, famotidine was similar in efficacy to cimetidine in the treatment of upper gastrointestinal bleeding and to ranitidine in the prevention of pulmonary aspiration of acid. In patients with Zollinger-Ellison syndrome, the potency and long duration of action of famotidine may confer an advantage over other H2-receptor antagonists--in individualised doses (mean 0.33 g/day) famotidine successfully controlled acid secretion for up to 72 months in 1 study of such patients. Accumulated clinical evidence confirms that famotidine is very well tolerated and is free of the antiandrogenic effects infrequently reported with cimetidine. Moreover, famotidine is not associated with altered hepatic metabolism of drugs. Thus, famotidine is an effective, well-tolerated alternative to cimetidine and ranitidine. Famotidine is also promising as maintenance therapy for preventing recurrence of duodenal ulcer and as initial or maintenance treatment of gastric hypersecretory disorders, but further clinical experience, particularly in the long term, is needed to define the relative efficacy and tolerability of famotidine in these indications.     

Effective treatment after failure of omeprazole plus amoxycillin to eradicate Helicobacter pylori infection in peptic ulcer disease

Methods: Fifty patients with relapsing or complicated Helicobacter pylori positive duodenal (n= 41) or gastric ulcer disease (n= 9) and failure of a combined treatment with omeprazole plus amoxycillin to eradicate H. pylori infection were re-treated with either oral triple therapy (bismuth subsalicylate, metronidazole, tetracycline) plus ranitidine [group I: n= 22] or high-dose omeprazole (40 mg b.d. to t.d.s.) plus amoxycillin (1 g t.d.s.) [group II: n= 28]. Results: Patients of group I and II had similar demographic and clinical characteristics. The overall proportion of eradication of H. pylori infection was 81.8% in group I and 78.6% in group II (P= N.S.) as judged from negative bacterial findings by means of an urease test, specific culture and histology after modified Giemsa stain. Ulcer healing was observed in all patients after a maximum duration of 10 weeks. Ten patients on triple therapy and only one patient on omeprazole plus amoxycillin (45.5%vs. 3.6%; P < 0.001) complained of side effects without necessity of discontinuation of the study medication in either group. Twenty patients (group I: n= 10: group II: n= 10) with relapsing duodenal ulcer disease and successful cure were prospectively followed for one year without any evidence of ulcer relapse or H. pylori re-infection. Conclusion: Oral triple therapy plus ranitidine or highdose omeprazole plus amoxycillin remain highly effective in eradicating H. pylori infection in patients with peptic ulcer disease and treatment failure of omeprazole/amoxycillin, but the omeprazole enhanced antibiotic monotherapy seems to be superior with regard to side effects. Thus, high-dose omeprazole/amoxycillin is recommended as the treatment of first choice in these selected patients. Triple therapy should be reserved for patients intolerant of amoxycillin     

A comparison of three doses of lansoprazole (15, 30 and 60 mg) and placebo in the treatment of duodenal ulcer

Background: Lansoprazole is a new proton pump inhibitor for the treatment of peptic ulcer disease. Methods: A double-blind, multicentre study was undertaken in 2 9 6 patients with endoscopically proven duodenal ulcer to compare the efficacy and safety of lansoprazole 15, 30 or 60 mg with placebo. Ulcer healing was documented by endoscopy at 2 and 4 weeks; patients whose ulcers healed after 4 weeks were followed for up to 6 months post-treatment. Results: Four-week healing rates of 89.4% 91.7% and 89.9% were obtained with lansoprazole 15, 30 and 60 mg, respectively, compared with 46.1 % on placebo (P < 0.001). All three doses of lansoprazole produced rapid symptom relief, although patients taking 60 mg lansoprazole required fewer antacids than did those taking 15 mg. At 6 months, the percentages of patients healed were 45.3%, 40.0% and 38.4% in the lansoprazole 15, 30 and 60 mg dosage groups, respectively, and 2 5.3 % for the placebo group. No significant adverse events were documented during the period of this trial. Conclusion: Lansoprazole is an effective and safe treatment for duodenal ulcer and the 15 mg dose is as effective as 30 or 60 mg.     

Lansoprazole versus famotidine: efficacy and tolerance in the acute management of duodenal ulceration

Lansoprazole (AG 1749/CG 4801) is an inhibitor of gastric acid secretion by blocking H+,K(+)-ATPase. In this 2:1 randomized, double-blind, multicentre trial lansoprazole 30 mg am was compared to 40 mg famotidine nocte in 264 out-patients suffering from uncomplicated duodenal ulcer. After 2 weeks of treatment ulcer healing was confirmed endoscopically in a significantly higher proportion (P = 0.027) of patients treated with lansoprazole (94/174 = 54.0%) compared to patients receiving famotidine (35/90 = 38.9%). Cumulative healing rates after 4 weeks were 91.4% for the lansoprazole group and 83.3% for the famotidine group (P = 0.065). Pain relief and decrease of concomitant antacid consumption during treatment were comparable in both groups. Both compounds were well tolerated. Rates of recurrent duodenal ulcer in the 6 months after trial treatment were 45/158 (28.5%) after lansoprazole, and 18/69 (26.1%) after famotidine.