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 versus ranitidine for the treatment of reflux oesophagitis

Background: Lansoprazole is a H⁺, K⁺-ATPase (proton pump) inhibitor with an anti-secretory action and is therefore potentially useful in the treatment of gastro-oesophageal reflux. Methods: This study was conducted to determine the efficacy and short-term safety of lansoprazole at doses of 30 mg or 60 mg once daily, compared with ranitidine 150 mg twice daily, in the treatment of patients with reflux oesophagitis. This was a double-blind, stratified, randomized, comparative, parallel group study conducted in five centres in the UK. A total of 229 patients (155 men) aged 18–79 years with endoscopically-confirmed oesophagitis were randomized to receive lansoprazole 30 mg p.o. daily, lansoprazole 60 mg p.o. daily, or ranitidine 150 mg p.o. b.d. Efficacy was assessed by endoscopic examination at 4 weeks and 8 weeks, together with symptom relief and antacid usage. Results: Lansoprazole 30 mg and 60 mg were superior at 4 and 8 weeks (P < 0.01) to ranitidine in healing reflux oesophagitis: respective healing rates being 84%, 72% and 39% after 4 weeks and 92%, 91% and 53% after 8 weeks. Relief of heartburn with lansoprazole 30 mg and 60 mg was superior to that achieved with ranitidine at both week 4 (P < 0.01) and week 8 (P < 0.02). Sixty-four patients experienced a total of 85 adverse events, one-third of which were considered drug-related. The incidence and severity were similar in the three groups. Conclusion: Lansoprazole 30 mg and 60 mg once daily are more effective than ranitidine 150 mg twice daily in the short-term treatment of reflux oesophagitis.     

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.     

A comparison of lansoprazole and ranitidine in the treatment of erosive oesophagitis

Background: Lansoprazole is a new proton pump inhibitor which produces prolonged decrease of gastric acidity. The aim of this study was to compare lansoprazole to a standard dose of ranitidine in the treatment of patients with reflux oesophagitis. Methods: Two hundred and forty-seven patients with erosive oesophagitis were randomly assigned to 8 weeks of treatment with either 30 mg lansoprazole once daily or 150 mg ranitidine twice daily. Results: Two hundred and forty-two patients were included in the analysis. Lansoprazole (30 mg) daily, healed oesophagitis in 92.1% of patients after 8 weeks of treatment. This was significantly superior to 150 mg ranitidine b.d.s. which healed oesophagitis in 69.9% of patients (P < 0.001). Relief of reflux symptoms was superior with lansoprazole to that with ranitidine. Both lansoprazole and ranitidine were well tolerated with no serious drug-related adverse events noted. Conclusion: Lansoprazole, 30 mg once daily, is highly effective and safe in the short-term treatment of erosive oesophagitis.     

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.     

Meta-analysis of randomized controlled trials comparing standard clinical doses of omeprazole and lansoprazole in erosive oesophagitis

BACKGROUND: Omeprazole and lansoprazole are used to treat erosive oesophagitis in the respective daily doses of 20 and 30 mg. AIM: To investigate, by meta-analysis, whether treatment with lansoprazole 30 mg increases erosive oesophagitis healing rates over omeprazole 20 mg. METHODS: We searched for randomized, double-blind trials comparing omeprazole 20 mg and lansoprazole 30 mg in endoscopically diagnosed erosive oesophagitis. After assessing for homogeneity, non-heterogeneous trials were combined and pooled healing rates derived. We calculated the relative benefit increase, absolute benefit increase and number needed to treat. RESULTS: Six trials without significant heterogeneity met predetermined inclusion criteria. By per protocol analysis, pooled healing rates for omeprazole 20 mg and lansoprazole 30 mg were, respectively, 74.7% and 77.7% after 4 weeks and 87.0% and 88.7% after 8 weeks. The corresponding figures by intention-to-treat analysis were 70.8% and 72.7% after 4 weeks and 81.8% and 83.3% after 8 weeks. In each analysis the absolute benefit increase for lansoprazole was small and its 95% confidence interval encompassed zero. CONCLUSION: Lansoprazole 30 mg produces healing rates in erosive oesophagitis that are not statistically significantly different to those of omeprazole 20 mg.     

Omeprazole is more effective than cimetidine for the relief of all grades of gastro-oesophageal reflux disease-associated heartburn, irrespective of the presence or absence of endoscopic oesophagitis

Background: Previous studies have demonstrated greater efficacy for omeprazole compared with cimetidine in patients with endoscopically verified oesophagitis, but excluded the substantial group of gastro-oesophageal reflux disease (GERD) patients with reflux symptoms but without endoscopic abnormality. This prospective, randomized, double-blind study compared omeprazole and cimetidine in the treatment of GERD-associated heartburn both in patients with symptomatic non-ulcerative oesophagitis and in those with heartburn but without oesophagitis. Methods: A total of 221 patients with heartburn and oesophageal mucosa grade 0 (normal, n = 51), 1 (no macroscopic erosions, n = 52), 2 (isolated erosions, n = 97) or 3 (confluent erosions, n = 21) were randomized to receive double-blind either omeprazole 20 mg daily or cimetidine 400 mg q.d.s. for a period of 4 weeks. Those still symptomatic after 4 weeks of treatment received omeprazole 20 mg daily for a further 4 weeks. Results: There was no correlation between severity of heartburn and endoscopic grade at entry (correlation coefficient = 0.196). After 4 weeks of treatment, the proportion of patients in whom heartburn was controlled (no more than mild symptoms on no more than 1 day in the previous 7) on omeprazole (66%; 74/112) was more than double that on cimetidine (31%; 34/109) (P < 0.0001). There was no significant difference between the relief of heartburn in the 47% of patients without unequivocal oesophagitis (endoscopic grade 0 or 1) and in the 53% of patients with erosive oesophagitis (grade 2 or 3) (P = 0.31). Only treatment with omeprazole (P < 0.0001) and lower severity of heartburn at entry (P < 0.01) were significant in predicting heartburn relief. Amongst those patients requiring an additional 4 weeks of treatment with omeprazole, 67% (54/81) reported that their heartburn was controlled after 8 weeks of treatment. Conclusion: We conclude that omeprazole is superior to cimetidine for the relief of all grades of heartburn in GERD, whether or not the patient has unequivocal endoscopic oesophagitis.     

A comparison of omeprazole, lansoprazole and pantoprazole in the maintenance treatment of severe reflux oesophagitis

Background:

Proton pump inhibitors are effective for the healing of oesophagitis. Standard doses of omeprazole, lansoprazole or pantoprazole are sufficient for healing in mild to moderate cases of oesophagitis.

Aim:

To compare the efficacy of double the standard doses of omeprazole, lansoprazole or pantoprazole for maintenance treatment of severe oesophagitis complicated by a stricture.

Methods:

Thirty-six patients with reflux oesophagitis and stricture confirmed by endoscopy were included in a prospective study comparing three maintenance therapies. In all cases weekly dilatation of the stenosis was performed and patients were treated with omeprazole 20 mg b.d. until healing of oesophagitis and dysphagia relief were achieved. Thirty participants responded to therapy and were then randomly assigned to 4 weeks of maintenance treatment with omeprazole (20 mg b.d.; n=10), lansoprazole (30 mg b.d.; n=10) or pantoprazole (40 mg b.d.; n=10). Subsequently, endoscopies were performed—the endoscopists were blinded to the therapy assignment. The endpoints were defined as the absence of oesophagitis, oesophageal stricture and complaints.

Results:

After 4 weeks of treatment, the number of patients remaining in remission (no oesophagitis or stricture and no symptoms) was nine out of 10 (90%) in the omeprazole group, two out of 10 (20%) in the lansoprazole group (P < 0.01) and three out of 10 (30%) in the pantoprazole group (P < 0.01).

Conclusions:

In our study omeprazole was superior to either lansoprazole or pantoprazole in the maintenance treatment of complicated gastro-oesophageal reflux disease.

     

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.     

Low-dose lansoprazole provides greater relief of heartburn and epigastric pain than low-dose omeprazole in patients with acid-related dyspepsia

AIM: To compare the relative efficacies of lansoprazole 15 mg o.m. and omeprazole 10 mg o.m. in relieving heartburn and epigastric pain in patients with acid-related dyspepsia. In addition, the study compared the safety profiles of the two treatments. METHODS: This double-blind, parallel group, randomised, multicentre study was conducted in 52 general practices in the UK. A total of 609 patients was recruited, 562 of whom were eligible for inclusion in the intention-to-treat analysis. All of the patients had experienced at least mild heartburn or mild epigastric pain persistently on at least 4 of the previous 7 days; patients with severe symptoms were excluded. 283 patients received lansoprazole 15 mg and 279 received omeprazole 10 mg, both for 4 weeks. The main efficacy measure was relief of symptoms, based on physician assessments. RESULTS: In the intention-to-treat population, a complete relief of overall primary symptoms of dyspepsia was achieved after 2 weeks in 53% of patients receiving lansoprazole and in 41% of patients receiving omeprazole (P = 0.007). After 4 weeks, 59% of the lansoprazole group and 51% of the omeprazole group had achieved complete symptom relief (P = 0. 078). Antacids were taken for additional relief of symptoms in fewer patients given lansoprazole compared to the omeprazole group in the third and fourth weeks (P = 0.035) and also significantly fewer antacids were taken by patients in the lansoprazole group compared with patients in the omeprazole group (P = 0.033). The proportion of patients reporting adverse events was similar in both groups. CONCLUSION: Low-dose lansoprazole is more effective than low-dose omeprazole in the treatment of patients with mild heartburn or epigastric pain in general practice.     

Pantoprazole and omeprazole in the treatment of reflux oesophagitis: a European multicentre study

Background: Pantoprazole is a new substituted benzimidazole which inhibits gastric H⁺,K⁺-ATPase. Methods: In this double-blind, multicentre study, pantoprazole 40 mg once daily was compared with omeprazole 20 mg once daily in the treatment of grade II and III (Savary–Miller) reflux oesophagitis. Endoscopy was repeated after 4 weeks of treatment, and also after 8 weeks in patients unhealed at 4 weeks. Results: The primary efficacy variable was ulcer healing; after 4 weeks, 81/103 (78.6%) patients in the pantoprazole group and 83/105 (79.0%) patients in the omeprazole group had healed completely. After 8 weeks, the cumulative healing rates were 94.2% and 91.4 % in the pantoprazole and omeprazole groups, respectively (P > 0.05 at 4 weeks and 8 weeks). Both groups experienced rapid relief of the key symptoms: heartburn, acid regurgitation and pain on swallowing. The time course of relief of the individual symptoms was similar in both groups after 2 and 4 weeks (P > 0.05). Both treatments were well tolerated, with only three patients withdrawing owing to adverse events. Conclusion: Pantoprazole has been shown to be as effective as omeprazole in the treatment of reflux oesophagitis.     

Standard-dose lansoprazole is more effective than high-dose ranitidine in achieving endoscopic healing and symptom relief in patients with moderately severe reflux oesophagitis. The Dutch Lansoprazole Study Group

BACKGROUND: In the treatment of reflux oesophagitis, H2-receptor antagonists are still widely used in spite of the apparent higher efficacy of proton pump inhibitors. In an attempt to compensate for the lower efficacy, H2-receptor antagonists are now increasingly being used at a higher dose. OBJECTIVE: To assess whether or not standard-dose lansoprazole (30 mg o.d.) is more effective than high-dose ranitidine (300 mg b.d.) in moderately severe reflux oesophagitis (grades II-III). METHODS: Lansoprazole or ranitidine was given to 133 patients for 4-8 weeks in a double-blind, randomized, parallel group, multicentre trial. RESULTS: The percentage of patients with endoscopically-verified healing was significantly higher on lansoprazole than on ranitidine both after 4 weeks (79% vs. 42%) and 8 weeks (91% vs. 66%), though smoking had a negative impact on oesophagitis healing with lansoprazole. Heartburn, retrosternal pain and belching improved significantly better with lansoprazole than with ranitidine, as did the patient-rated overall symptom severity. Relief of heartburn appeared somewhat faster with ranitidine, but was more pronounced with lansoprazole. The number of patients with adverse events was similar in both treatment groups. CONCLUSION: Standard-dose lansoprazole is better than high-dose ranitidine in moderately severe reflux oesophagitis.     

Daily omeprazole surpasses intermittent dosing in preventing relapse of oesophagitis: a US multi-centre double-blind study

Introduction: Relapse of erosive oesophagitis occurs in almost all patients if treatment is stopped after initial healing. Aim: To assess the potential of different therapeutic regimens of omeprazole to prevent relapse of erosive reflux oesophagitis after initial healing with omeprazole. Patients and methods: Patients whose active erosive reflux oesophagitis (grade 2) had healed (grade 0 or 1) after 4–8 weeks of open-label omeprazole 40 mg daily (phase I) were eligible to join a multi-centre, 6-month double-blind, placebo-controlled maintenance study (phase II), which included endoscopy, symptom assessments, serum gastrin measurements, and gastric fundic biopsies. During phase I, endoscopy was performed at weeks 0, 4, and 8. At the end of phase I, 429 of 472 patients (91%) were healed, and there were significant reductions in heartburn, dysphagia and acid regurgitation. Of the 429 patients who healed, 406 joined phase II and were randomized to one of three groups: 20 mg omeprazole daily (n=138), 20 mg omeprazole for 3 consecutive days each week (n=137), or placebo (n=131). During phase II, endoscopy was performed at months 1, 3, and 6 or at symptomatic relapse. Results: The percentages of patients still in endoscopic remission at 6 months were 11% for placebo, 34% for omeprazole 3-days-a-week, and 70% for omeprazole daily. Both omeprazole regimens were superior to placebo in preventing recurrence of symptoms (P<0.001); however, omeprazole 20 mg daily was superior to omeprazole 20 mg 3-days-a-week (P<0.001). Compared to baseline, omeprazole therapy resulted in no significant differences among treatment groups in the distribution of gastric endocrine cells. Conclusions: These results show that after healing of erosive oesophagitis with 4–8 weeks of omeprazole, relapse of oesophagitis and recurrence of reflux symptoms can be prevented in 70% of patients with a maintenance regimen of 20 mg daily, but that intermittent dosing comprising 3 consecutive days each week significantly compromises efficacy.     

Does 40 mg omeprazole daily offer additional benefit over 20 mg daily in patients requiring more than 4 weeks of treatment for symptomatic reflux oesophagitis?

This study was designed to establish whether 40 mg omeprazole once daily exhibits sufficient additional efficacy over that of 20 mg omeprazole once daily in patients with symptomatic reflux oesophagitis requiring more than an initial 4-week course of 20 mg omeprazole once daily (o.m.) to warrant routine use of the higher dose. Three hundred and thirteen patients were randomized to receive either 20 mg omeprazole (4 weeks) then 20 mg (second 4 weeks if not both healed and symptom-free after 4 weeks), or 20 mg omeprazole (4 weeks) then 40 mg omeprazole o.m. (second 4 weeks). One hundred and twenty-seven patients were healed and symptom-free after 4 weeks and left the study at that point. Taking the second treatment period in isolation, the healing rate (64%vs. 45%, P < 0.02) and relief of heartburn (72%vs. 60%, P < 0.002) were greater among patients receiving 40 mg omeprazole o.m., demonstrating the existence of a dose–response relationship for omeprazole. However, on completion, there were no significant differences between the patients randomized to the 20/20 mg (healed 65%, asymptomatic 69%) or the 20/40 mg (healed 74%, asymptomatic 74%: both not significant differences compared with 20/20 mg) regimens. The magnitude of the difference in efficacy between 20 and 40 mg omeprazole in symptomatic reflux oesophagitis is insufficient to warrant the routine use of 40 mg in patients requiring more than 4 weeks' treatment with 20 mg omeprazole o.m.; continued treatment with 20 mg omeprazole for 4–8 weeks is the preferred option.     

Race affects healing of erosive oesophagitis in patients treated with proton pump inhibitors

Aliment Pharmacol Ther 2011; 34: 487–493

Summary

Background Erosive oesophagitis appears to be more common in white vs. nonwhite patients with gastro‐oesophageal reflux disease (GERD). Aim To evaluate the association between race and erosive oesophagitis healing in patients with GERD treated with once‐daily proton pump inhibitors (PPIs). Methods Data from five double‐blind trials of once‐daily treatment with esomeprazole 40 mg vs. omeprazole 20 mg or lansoprazole 30 mg for erosive oesophagitis healing (evaluated at weeks 4 and 8 by endoscopy) were pooled and stratified by baseline race and Los Angeles (LA) severity grade. Multiple logistic regression models were fit with erosive oesophagitis healing (dependent variable) and race (independent variable), with adjustments for treatment, study, baseline LA grade, age, gender, BMI, Helicobacter pylori status, hiatal hernia and interactions of these factors with race. Results Of 11 027 patients, 91% were white. Nonwhite (n = 978) and black (n = 613) patients were less likely to have severe baseline erosive oesophagitis (LA grade C or D) than white patients [adjusted OR: 0.69 (95% CI, 0.61–0.79) and 0.67 (0.57–0.78), respectively; P < 0.0001]. At week 8, nonwhite and black patients had lower healing rates than white patients [OR: 0.75 (0.63–0.89) and 0.67 (0.54–0.83), respectively; P ≤ 0.001]. Greater odds of healing were associated with less severe baseline LA grade, increasing age, hiatal hernia, esomeprazole treatment (vs. lansoprazole or omeprazole) and lansoprazole treatment (vs. omeprazole) (all P ≤ 0.0009); no factor interacted significantly with race. Conclusions Nonwhite patients with GERD had less severe baseline erosive oesophagitis, but were less likely than white patients to have erosive oesophagitis healing after 8‐week PPI therapy.     

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.     

Clinical trial: factors associated with resolution of heartburn in patients with reflux oesophagitis – results from the EXPO study

Background The ability to predict symptom response to reflux oesophagitis‐healing therapy may optimize treatment decisions. Aim To identify factors associated with heartburn resolution in patients receiving acid‐suppressive therapy for reflux oesophagitis. Methods In this multicentre, randomized, double‐blind trial (EXPO; AstraZeneca study code: SH‐NEG‐0008), patients with endoscopically confirmed reflux oesophagitis and reflux symptoms received once‐daily proton pump inhibitor therapy [esomeprazole 40 mg (n = 1562) or pantoprazole 40 mg (n = 1589)] for ≥4 weeks. Factors associated with heartburn resolution after 4 weeks were identified by multiple logistic regression analysis. Results Esomeprazole therapy, positive Helicobacter pylori status and greater age were associated with an increased likelihood of heartburn resolution [odds ratio (95% confidence interval): 1.31 (1.12, 1.54), 1.44 (1.19, 1.74) and 1.013 (1.007, 1.019) per year, respectively; all P < 0.001]. Men and patients with no acid regurgitation or epigastric pain pre‐treatment were also more likely to achieve heartburn resolution (all P < 0.05). Conclusions The use of esomeprazole rather than pantoprazole increases the probability of achieving resolution of heartburn during reflux oesophagitis‐healing therapy. Other factors, including H. pylori status, age, gender and symptom profile may be helpful in determining the likelihood of heartburn resolution in such patients.     

Treatment and prevention of relapse of mild oesophagitis with omeprazole and cisapride: comparison of two strategies

Background: Oesophagitis is usually a chronic condition. Healing with omeprazole is often followed by early relapse. Combination treatment and subsequent maintenance treatment with the prokinetic cisapride may be of benefit in relapse prevention. Methods: Patients with endoscopically proven oesophagitis, grade I (n= 120) or grade II (n= 105), were randomized in an open fashion to receive 8 weeks of healing treatment with omeprazole 20 mg daily (OM) followed by 12 months of follow-up without maintenance treatment, or 8 weeks of combined treatment of omeprazole 20 mg daily plus cisapride 5 mg t.d.s. (OMCIS) followed by 12 months of maintenance treatment with cisapride 5 mg t.d.s. (CIS). Only the patients healed after acute treatment were included in the 12-month follow-up study for evaluation of endoscopic relapse. Results: In the group of patients with oesophagitis grade I (n= 58 receiving OM, n= 62 receiving OMCIS), healing rates were comparable for both acute treatment regimens. In the group of patients with grade II (n= 54 receiving OM, n= 51 receiving OMCIS), the healing rates were slightly but not significantly in favour of OMCIS after 4 and 8 weeks of treatment. During the 12 months of follow-up, CIS maintenance treatment was associated with a significant reduction of relapse. In the group of patients with initial grade I oesophagitis, the relapse rates after 3 months were 20% in the OMCIS group receiving CIS maintenance treatment, compared to 48 % in the group healed on OM without further maintenance treatment (P= 0.04). After 6 months, these relapse rates were 31% and 85% respectively (P < 0.001), and after 12 months 40% and 96% (P < 0.001). In the group of patients with initial grade II oesophagitis, they were, respectively, 20% vs. 39% after 3 months (P= 0.056), 41% vs. 78% after 6 months (P < 0.001) and 52% vs. 95 % after 12 months (P < 0.001). Conclusions: The results of this open study indicate that continued treatment with cisapride 5 mg t.d.s. (after initial healing with omeprazole 20 mg daily plus cisapride 5 mg t.d.s.) is beneficial in the long-term management of grade I and II oesophagitis : this treatment approach significantly reduces the high relapse rate observed after stopping healing treatment with omeprazole.     

Lansoprazole for maintenance of remission of erosive oesophagitis

Gastro-oesophageal reflux disease, which is experienced daily by a significant proportion of individuals, may result in serious sequelae such as erosive oesophagitis. Short-term treatment with acid antisecretory therapy (a proton pump inhibitor or a histamine H(2) receptor antagonist) is highly effective in healing the erosive oesophagitis lesion. However, numerous studies confirm that unless maintenance therapy is initiated virtually all patients will experience oesophagitis relapse within 1 year, as well as an increasing severity of oesophagitis and risk for complications such as Barrett's oesophagus and adenocarcinoma. Studies evaluating the efficacy of proton pump inhibitor and H(2) antagonist maintenance therapy have found that only the proton pump inhibitors significantly reduce the incidence of oesophagitis relapse. Pharmacoeconomic studies have also confirmed that proton pump inhibitor maintenance therapy is cost effective, by virtue of the ability of these agents to reduce the incidence of relapse as well as prolong the time to relapse and increase the number of weeks per year that patients are without symptoms. Lansoprazole, a member of the proton pump inhibitor class of agents, has been extensively studied in the treatment of patients with a variety of acid-related disorders. Among those with erosive oesophagitis, maintenance therapy with lansoprazole 15 or 30mg once daily is highly effective in preventing relapse. Studies have documented that lansoprazole 15 and 30mg once daily for six months prevents oesophagitis relapse in up to 81 and 93% of patients, respectively, with comparable percentages of patients remaining in remission after 1 year of treatment. These high rates of remission have also been observed in studies of patients with lesions that were difficult to heal at baseline (resistant to healing with at least 3 months of H(2) antagonist therapy). Moreover, lansoprazole produces high remission rates regardless of the grade of erosive oesophagitis before acute healing. Among symptomatic patients with heartburn, lansoprazole provides rapid and effective relief of daytime and night-time heartburn and prevents relapse of symptoms. Lansoprazole has a wide margin of safety and is well tolerated when administered as monotherapy in short- and long-term clinical trials. Taken together these data suggest that proton pump inhibitor therapy represents the preferred and ideal long-term management strategy for the patient with erosive oesophagitis. Lansoprazole is a well-established member of this class of agents and, as such, has an extensive body of literature that supports its safety, tolerability and clinical efficacy in preventing relapse in these patients.