Esomeprazole: a review of its use in the management of acid-related disorders

Esomeprazole (S-isomer of omeprazole), the first single optical isomer proton pump inhibitor, generally provides better acid control than current racemic proton pump inhibitors and has a favourable pharmacokinetic profile relative to omeprazole. In a large well designed 8-week trial in patients (n >5000) with erosive oesophagitis, esomeprazole recipients achieved significantly higher rates of endoscopically confirmed healed oesophagitis than those receiving lansoprazole. Respective healed oesophagitis rates with once-daily esomeprazole 40mg or lansoprazole 30mg were 92.6 and 88.8%. Overall, esomeprazole was also better than omeprazole, although these differences were not always statistically significance. Ninety-two to 94% of esomeprazole recipients (40mg once daily) achieved healed oesophagitis versus 84 to 90% of omeprazole recipients (20mg once daily). Esomeprazole was effective across all baseline grades of oesophagitis; notably, relative to lansoprazole, as baseline severity of disease increased, the difference in rates of healed oesophagitis also increased in favour of esomeprazole. Resolution of heartburn was also significantly better with esomeprazole 40mg than with these racemic proton pump inhibitors. Long-term (up to 12 months) therapy with esomeprazole effectively maintained healing in these patients. Once-daily esomeprazole 20 or 40mg for 4 weeks resolved symptoms in patients with symptomatic gastro-oesophageal reflux disease (GORD) without oesophagitis. Symptoms were effectively managed in the long-term with symptom-driven on-demand esomeprazole (20 or 40mg once daily). Eradicating Helicobacter pylori infection is considered pivotal to successfully managing duodenal ulcer disease. Seven days' treatment (twice-daily esomeprazole 20mg plus amoxicillin 1g and clarithromycin 500mg) eradicated H. pylori in >/=86% of patients (intention-to-treat), a rate that was similar to equivalent omeprazole-based regimens. Esomeprazole is generally well tolerated, both as monotherapy and in combination with antimicrobial agents, with a tolerability profile similar to that of other proton pump inhibitors. Few patients discontinued therapy because of treatment-emergent adverse events (<3% of patients), with very few (<1%) drug-related serious adverse events reported. CONCLUSIONS: Esomeprazole is an effective, well tolerated treatment for managing GORD and for eradicating H. pylori infection in patients with duodenal ulcer disease. In 8-week double-blind trials, esomeprazole healed oesophagitis and resolved symptoms in patients with endoscopically confirmed erosive oesophagitis and overall, provided better efficacy than omeprazole. Notably, in a large (n >5000 patients) double-blind trial, esomeprazole 40mg provided significantly better efficacy than lansoprazole in terms of healing rates and resolution of symptoms. Long-term therapy with esomeprazole maintained healed oesophagitis in these patients. Esomeprazole also proved beneficial in patients with symptomatic GORD without oesophagitis. Thus, esomeprazole has emerged as an option for first-line therapy in the management of acid-related disorders.     

Esomeprazole

Esomeprazole, a new proton pump inhibitor, is the S-isomer of omeprazole and is the first such inhibitor to be developed as a single isomer. Esomeprazole provided better control of intragastric pH than omeprazole, lansoprazole and pantoprazole in trials conducted in patients with gastro-oesophageal reflux disease (GORD) or healthy volunteers (n = 20 to 115). In 2 large randomised, double-blind multicentre trials esomeprazole 20 and/or 40mg for 8 weeks produced higher healing rates of erosive oesophagitis and better symptom control than omeprazole 20 mg in patients with GORD. Esomeprazole 10, 20 or 40mg once daily for 6 months maintained healing versus placebo (p < 0.001) in patients with endoscopically confirmed healed erosive oesophagitis in 2 large randomised, double-blind multicentre trials. Similarly, symptom-driven on-demand use of esomeprazole effectively controlled symptoms of GORD (heartburn) for 6 months in 2 large placebo-controlled trials. Esomeprazole-based triple therapy for 7 days was as effective for eradication of Helicobacter pylori as longer omeprazole-based therapy in 2 randomised double-blind trials including about 450 patients each. Endoscopically confirmed ulcer healing 4 weeks after treatment initiation was reported in about 90% of patients with active duodenal ulcer in both treatment groups. Esomeprazole-based triple therapy for 10 days was more effective than esomeprazole plus clarithromycin for eradication of H. pylori in 233 patients.     

Review of esomeprazole in the treatment of acid disorders

Esomeprazole (Nexium, AstraZeneca) is the (S)-isomer of omeprazole and the first proton pump inhibitor to be developed as an optical isomer. Esomeprazole has an improved pharmacokinetic profile, resulting in increased systemic exposure and less interindividual variability compared with omeprazole, and more effective suppression of gastric acid production compared with other proton pump inhibitors. In several large, double-blind, randomised trials, significantly higher rates of endoscopically-confirmed healing of erosive oesophagitis and resolution of heartburn have been achieved in patients with gastro-oesophageal reflux disease receiving 8 weeks of esomeprazole 40 mg o.d. compared with those receiving omeprazole 20 mg o.d. or lansoprazole 30 mg o.d. In the maintenance of healed erosive oesophagitis, esomeprazole 10, 20 or 40 mg o.d. was significantly more effective than placebo in two 6-month, randomised, double-blind trials. Additionally, esomeprazole 20 mg o.d. was more effective than lansoprazole 15 mg in the maintenance of healed erosive oesophagitis in another 6-month, randomised, double-blind trial. Healing of oesophagitis was also effectively maintained by esomeprazole 40 mg o.d. in a 12-month non-comparative trial. Esomeprazole 20 or 40 mg o.d. effectively relieved heartburn in patients with gastro-oesophageal reflux disease without oesophagitis in two 4-week, placebo-controlled trials. Clinical trials have shown that triple therapy with esomeprazole 40 mg o.d. in combination with amoxicillin and clarithromycin produced Helicobacter pylori eradication rates similar to those obtained using triple therapy involving twice-daily dosing with other proton pump inhibitors. Esomeprazole is well-tolerated, with a spectrum and incidence of adverse events similar to those associated with omeprazole.     

Esomeprazole 20 mg and lansoprazole 15 mg in maintaining healed reflux oesophagitis: Metropole study results

AIM: To compare the efficacy of esomeprazole, 20 mg once daily, vs. lansoprazole, 15 mg once daily, for the maintenance treatment of patients with healed reflux oesophagitis. METHODS: During the initial open healing phase, 1391 patients with endoscopically verified reflux oesophagitis and a history of heartburn, with or without acid regurgitation, received esomeprazole 40 mg for 4-8 weeks. Patients who were healed (identified by endoscopy at 4 or 8 weeks) and symptom free were then randomized to receive 6 months of treatment with esomeprazole, 20 mg once daily, or lansoprazole, 15 mg once daily. RESULTS: Esomeprazole, 20 mg once daily, maintained a significantly higher proportion of patients in remission than lansoprazole, 15 mg once daily, over 6 months [83% (95% CI, 80-86%) of esomeprazole recipients compared with 74% (95% CI, 70-78%) of lansoprazole recipients; P < 0.0001; life table estimates]. When data were analysed according to baseline Los Angeles grade classification, esomeprazole, 20 mg once daily, achieved consistently higher remission rates across all grades of disease severity, whereas the efficacy of lansoprazole decreased to a greater extent with increasing severity of reflux oesophagitis. CONCLUSION: Esomeprazole, 20 mg once daily, is more effective than lansoprazole, 15 mg once daily, in maintaining remission in patients with healed reflux oesophagitis.     

Review article: esomeprazole in the treatment of Helicobacter pylori

Proton pump inhibitor-based triple therapy is the most commonly used treatment for eradication of Helicobacter pylori, with pooled eradication rates of approximately 90%. In the USA, per protocol eradication rates with 10-day proton pump inhibitor-based triple therapy are approximately 85%. Esomeprazole, a new proton pump inhibitor that is the S-isomer of omeprazole and produces a greater inhibition of acid secretion than omeprazole, has recently been evaluated in the treatment of H. pylori. Seven-day twice daily triple therapy with esomeprazole 20 mg, amoxicillin 1 g and clarithromycin 500 mg provided intention-to-treat eradication rates of 86-90% and per protocol eradication rates of 90-91% in duodenal ulcer patients in Europe and Canada. Ten-day triple therapy with esomeprazole 40 mg q.d.s., amoxicillin 1 g b.d. and clarithromycin 500 mg b.d. achieved intention-to-treat eradication rates of 77-78% and per protocol eradication rates of 84-85% in USA duodenal ulcer patients. Thus, esomeprazole triple therapy with amoxicillin and clarithromycin is effective in the treatment of H. pylori, with eradication rates comparable to previously studied proton pump inhibitor-based triple therapies.     

The new proton pump inhibitor esomeprazole is effective as a maintenance therapy in GERD patients with healed erosive oesophagitis: a 6-month, randomized, double-blind, placebo-controlled study of efficacy and safety

BACKGROUND: Esomeprazole, the S-isomer of omeprazole, is the first proton pump inhibitor to be developed as an optical isomer. In patients with erosive oesophagitis, esomeprazole has produced significantly greater healing rates and improved symptom resolution vs. omeprazole. AIM: This study assesses the efficacy of esomeprazole for preventing relapse in patients with healed oesophagitis. METHODS: In this 6-month US multicentre randomized double-blind placebo-controlled trial, 375 Helicobacter pylori-negative patients with endoscopically healed oesophagitis received esomeprazole 40 mg, 20 mg, 10 mg, or placebo once daily. The primary efficacy end-point was maintenance of healing at 6 months. Secondary end-points assessed changes in symptoms, and long-term safety and tolerability. RESULTS: Significantly (P < 0.001) more patients remained healed with esomeprazole 40 mg (87.9%), 20 mg (78.7%), or 10 mg (54.2%), than with placebo (29.1%). Relapse, when it occurred, was later with esomeprazole. Sustained resolution of heartburn was observed in the 40 mg and 20 mg groups; there was a high correlation between absence of heartburn and maintenance of healing. Adverse effects were mild, infrequent and not significantly different between groups. CONCLUSIONS: Esomeprazole is effective and well-tolerated in the maintenance of healing of erosive oesophagitis. Esomeprazole 40 mg and 20 mg offer significant clinical benefit to patients.     

Esomeprazole in the treatment of Helicobacter pylori

Proton pump inhibitor-based triple therapy is the most commonly used treatment for eradication of Helicobacter pylori , with pooled eradication rates of approximately 90%. In the USA, per protocol eradication rates with 10-day proton pump inhibitor-based triple therapy are approximately 85%. Esomeprazole, a new proton pump inhibitor that is the S-isomer of omeprazole and produces a greater inhibition of acid secretion than omeprazole, has recently been evaluated in the treatment of H. pylori . Seven-day twice daily triple therapy with esomeprazole 20 mg, amoxicillin 1 g and clarithromycin 500 mg provided intention-to-treat eradication rates of 86–90% and per protocol eradication rates of 90–91% in duodenal ulcer patients in Europe and Canada. Ten-day triple therapy with esomeprazole 40 mg q.d.s., amoxicillin 1 g b.d. and clarithromycin 500 mg b.d. achieved intention-to-treat eradication rates of 77–78% and per protocol eradication rates of 84–85% in USA duodenal ulcer patients. Thus, esomeprazole triple therapy with amoxicillin and clarithromycin is effective in the treatment of H. pylori , with eradication rates comparable to previously studied proton pump inhibitor-based triple therapies.     

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: 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.     

Esomeprazole: a review of its use in the management of gastric acid-related diseases in adults

Esomeprazole (Nexium); S-omeprazole) is a single optical isomer proton-pump inhibitor (PPI) approved for the management of reflux oesophagitis, the symptomatic treatment of gastro-oesophageal reflux disease (GORD), the prevention and healing of NSAID-associated gastric ulcer disease (and the prevention of NSAID-associated duodenal ulcers in the UK), the treatment of Helicobacter pylori infection and associated duodenal ulcer disease (and prevention of relapse of H. pylori-associated peptic ulcers in the UK), and the treatment of Zollinger-Ellison syndrome (and other hypersecretory syndromes in the US).Once-daily oral esomeprazole 40 mg demonstrates greater antisecretory activity than other PPIs. Overall, in well designed clinical studies of 4 weeks' to 6 months' duration in patients with GORD, esomeprazole had similar or better efficacy than other agents. In patients requiring ongoing treatment with NSAIDs, co-therapy with once-daily esomeprazole 20 or 40 mg achieved relief of gastrointestinal symptoms or prevented ulcer occurrence, more effectively than placebo. Esomeprazole was also better than ranitidine 150 mg twice daily in healing NSAID-associated gastric ulcers. In addition, the drug has demonstrated efficacy as part of a triple-therapy regimen for the eradication of H. pylori infection, the healing of H. pylori associated duodenal ulcers and the prevention of relapse of gastric ulcers. Esomeprazole also effectively treated patients with Zollinger-Ellison syndrome. Esomeprazole is generally well tolerated with an adverse-event profile similar to that of other PPIs. Thus, the efficacy and tolerability of esomeprazole for the management of GORD and H. pylori eradication remains undisputed, and the data support its use for the first-line treatment of NSAID-associated gastric ulcer disease and Zollinger-Ellison syndrome.     

Pantoprazole: an update of its pharmacological properties and therapeutic use in the management of acid-related disorders

Pantoprazole (Protonix) is an irreversible proton pump inhibitor (PPI) that reduces gastric acid secretion. In combination with two antimicrobial agents (most commonly metronidazole, clarithromycin or amoxicillin) for 6-14 days, pantoprazole 40 mg twice daily produced Helicobacter pylori eradication rates of 71-93.8% (intent-to-treat [ITT] or modified ITT analysis) in patients without known antibacterial resistance. Pantoprazole-containing triple therapy was at least as effective as omeprazole- and similar in efficacy to lansoprazole-containing triple therapy in large trials. In the treatment of moderate to severe gastro-oesophageal reflux disease (GORD), oral pantoprazole 40 mg/day was as effective as other PPIs (omeprazole, omeprazole multiple unit pellet system, lansoprazole and esomeprazole) and significantly more effective than histamine H(2)-antagonists. Pantoprazole 20 mg/day provided effective mucosal healing in patients with GORD and mild oesophagitis. Intravenous pantoprazole 40 mg/day can be used in patients who are unable to take oral medication. Oral pantoprazole 20-40 mg/day for up to 24 months prevented relapse in most patients with healed GORD. According to preliminary data, oral pantoprazole 20 or 40 mg/day was effective at healing and preventing non-steroidal anti-inflammatory drug (NSAID)-related ulcers, and intravenous pantoprazole was at least as effective as intravenous ranitidine in preventing ulcer rebleeding after endoscopic haemostasis. Oral or intravenous pantoprazole up to 240 mg/day maintained target acid output levels in most patients with hypersecretory conditions, including Zollinger-Ellison syndrome. Oral and intravenous pantoprazole appear to be well tolerated in patients with acid-related disorders in short- and long-term trials. Tolerability with oral pantoprazole was similar to that with other PPIs or histamine H(2)-antagonists in short-term trials. Formal drug interaction studies have not revealed any clinically significant interactions between pantoprazole and other agents. In conclusion, pantoprazole is an effective agent in the management of acid-related disorders. As a component of triple therapy for H. pylori eradication and as monotherapy for the healing of oesophagitis and maintenance of GORD, pantoprazole has shown similar efficacy to other PPIs and greater efficacy than histamine H(2)-antagonists. Limited data suggest that it is also effective in Zollinger-Ellison syndrome and in preventing ulcer rebleeding. Pantoprazole is well tolerated with minimal potential for drug interactions. The availability of pantoprazole as both oral and intravenous formulations provides flexibility when the oral route of administration is not appropriate. Thus, pantoprazole is a valuable alternative to other PPIs in the treatment of acid-related disorders.     

4种质子泵抑制剂治疗胃食管反流病的临床观察

目的:比较4种质子泵抑制剂埃索美拉唑(esomeprazole)、奥美拉唑(omeprazole)、兰索拉唑(lansoprazole)和雷贝拉唑(rabeprazole)对胃食管反流病(GERD)患者,在胃酸分泌、控制症状、治愈食管炎等方面的影响。方法:将经胃镜诊断明确的124例GERD患者随机分为A,B,C,D 4组,分别给予埃索美拉唑40 mg·d~(-1),奥美拉唑40 mg·d~(-1),兰索拉唑30 mg·d~(-1),雷贝拉唑20 mg·d~(-1),qd,疗程均为4周。结果:4种质子泵抑制剂症状缓解率分别为93.1%,81.6%,85.7%和86.4%,内镜下食管炎治愈率在70%以上(P<0.05)。结论:埃索美拉唑在症状缓解率和内镜下食管炎治愈率明显优于其他3种质子泵抑制剂。     

Rabeprazole: an update of its use in acid-related disorders.

Rabeprazole is an inhibitor of the gastric proton pump. It causes dose-dependent inhibition of acid secretion. In 8-week studies, among patients with gastro-oesophageal reflux disease (GORD), rabeprazole 20 mg/day or 10mg twice daily was as effective as omeprazole and superior to ranitidine in the healing of GORD. Symptom relief with rabeprazole was superior to that provided by placebo and ranitidine and similar to omeprazole. In long-term trials rabeprazole 10 mg/day was similar to omeprazole 20 mg/day in a 2-year study and superior to placebo in 1-year studies, in both the maintenance of healing and prevention of symptoms in patients with healed GORD. In nonerosive GORD, 4-week studies have shown rabeprazole to be more effective than placebo in relieving heartburn and various other gastrointestinal symptoms. Data among patients with Barrett's oesophagus suggest rabeprazole 20 mg/day may be more effective than placebo in maintaining healing of associated oesophagitis after 1 year of treatment. One-week triple Helicobacter pylori eradication therapy with rabeprazole plus clarithromycin and amoxicillin achieved eradication rates of > or =85%. Rabeprazole is as effective as omeprazole and lansoprazole when included as part of a triple-therapy regimen for the eradication of H. pylori. Eradication rates of >90% were achieved when rabeprazole 20 to 40 mg/day was included as part of a quadruple eradication regimen. As monotherapy for peptic ulcer healing and symptom relief, 4- to 8-week studies have shown rabeprazole 10 to 40 mg/day to be superior to placebo and ranitidine and have similar efficacy to omeprazole. Preliminary 1-year data among 16 patients with Zollinger-Ellison syndrome suggest rabeprazole 60 to 120 mg/day can resolve and prevent the recurrence of symptoms and endoscopic lesions associated with this condition. In clinical trials of up to 2 years' duration the tolerability of rabeprazole is similar to that of placebo, ranitidine and omeprazole. Common adverse events assigned to rabeprazole have been diarrhoea, headache, rhinitis, nausea, pharyngitis and abdominal pain. Histological changes and increases in serum gastrin levels were unremarkable and typical of proton pump inhibitors. No dosage adjustment is necessary in renal and mild to moderate hepatic impairment. CONCLUSION: Rabeprazole is a well tolerated proton pump inhibitor. It has proven efficacy in healing, symptom relief and prevention of relapse of peptic ulcers and GORD and can form part of effective H. pylori eradication regimens. It is an important alternative to H(2) antagonists and an additional treatment option to other proton pump inhibitors in the management of acid-related disorders.     

Cost effectiveness of esomeprazole compared with omeprazole in the acute treatment of patients with reflux oesophagitis in the UK

BACKGROUND: Clinical studies have demonstrated that esomeprazole is superior to omeprazole for the acute treatment of reflux oesophagitis. OBJECTIVE: To compare the cost effectiveness of esomeprazole 40mg once daily with omeprazole 20mg once daily in patients with reflux oesophagitis. METHODS: Pooled data were used from three 8-week clinical trials comparing the efficacy and safety of esomeprazole 40mg once daily and omeprazole 20mg once daily for the acute treatment of reflux oesophagitis. A simple decision analysis model, using UK direct medical costs, compared the cost effectiveness of the two treatments. Healing probabilities derived from the clinical studies using the Life Table method were used to estimate the effectiveness and cost of treating 100 patients with reflux oesophagitis. Patient management assumptions were based on a clinical management survey involving 25 UK physicians. PERSPECTIVE: UK National Health Service. RESULTS: After 4 weeks' therapy, the Life Table estimated the oesophageal healing rate to be 77.7% in esomeprazole 40mg once-daily recipients (n = 2446), compared with 67.6% in omeprazole 20mg once-daily recipients (n = 2431; p < 0.001). The corresponding values after 8 weeks' treatment were 93.4% and 86.2%, respectively (p < 0.001). The model predicted that when considering healing probabilities over 8 weeks, esomeprazole 40mg once daily produced total direct cost savings of pound1290 (14%) when compared with omeprazole 20mg once daily. When considering the cost of treating patients who had failed treatment (defined as patient not healed as assessed by endoscopy) after 8 weeks, the cost advantage for esomeprazole was even greater. CONCLUSION: Esomeprazole 40mg once daily is cost effective compared with omeprazole 20mg once daily in the acute treatment of patients with reflux oesophagitis; esomeprazole provides greater effectiveness at a lower cost.     

Review article: Esomeprazole--enhanced bio-availability,specificity for the proton pump and inhibition of acid secretion

Esomeprazole, the S-isomer of omeprazole, is the first proton pump inhibitor available for clinical use as a single isomer. It demonstrates pharmacological and clinical benefits beyond those seen with the racemic omeprazole. Esomeprazole has higher and more consistent bio-availability than omeprazole, which results in a greater area under the plasma concentration-time curve. It is the area under the plasma concentration-time curve of omeprazole and esomeprazole that determines how much of each reaches the parietal cell, and thus the control of gastric acid secretion that is achieved. Esomeprazole, like other proton pump inhibitors, has a high specificity for the acidic environment of the parietal cell, where it is accumulated, activated and covalently inhibits the proton pump. Proton pumps elsewhere in the body do not achieve the level of acidity needed for accumulation and activation. Esomeprazole, 40 mg once daily, provides more effective control of gastric acid secretion than omeprazole, 20 or 40 mg once daily, and all other proton pump inhibitors given at their standard doses. This translates into greater clinical effect compared with omeprazole, 20 mg once daily, and lansoprazole, 30 mg once daily, in the management of reflux disease. Esomeprazole therapy is well tolerated, with a low adverse events profile, similar to that seen with omeprazole.     

Esomeprazole improves healing and symptom resolution as compared with omeprazole in reflux oesophagitis patients: a randomized controlled trial. The Esomeprazole Study Investigators

BACKGROUND: The pharmacologic profile of the new proton pump inhibitor esomeprazole has demonstrated advantages over omeprazole that suggest clinical benefits for patients with acid-related disease. METHODS: 1960 patients with endoscopy-confirmed reflux oesophagitis (RO) were randomized to once daily esomeprazole 40 mg (n=654) or 20 mg (n=656), or omeprazole 20 mg (n=650), the standard recommended dose for RO, for up to 8 weeks in a US, multicentre, double-blind trial. The primary efficacy variable was the proportion of patients healed at week 8. Secondary variables included healing and heartburn resolution at week 4, time to first resolution and sustained resolution of heartburn, and per cent of heartburn-free days and nights. Safety and tolerability were also evaluated. RESULTS: Significantly more patients were healed at week 8 with esomeprazole 40 mg (94.1%) and 20 mg (89.9%) vs. omeprazole 20 mg (86.9%), using cumulative life table estimates, ITT analysis (each P < 0.05). Esomeprazole 40 mg was also significantly more effective than omeprazole for healing at week 4 and for all secondary variables evaluating heartburn resolution. The most common adverse events in all treatment groups were headache, abdominal pain and diarrhoea. CONCLUSION: Esomeprazole was more effective than omeprazole in healing and symptom resolution in GERD patients with reflux oesophagitis, and had a tolerability profile comparable to that of omeprazole.     

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.     

Systematic review of proton pump inhibitors for the acute treatment of reflux oesophagitis

BACKGROUND: Esomeprazole is a new proton pump inhibitor, which has been compared to omeprazole for the treatment of reflux oesophagitis in clinical trials. AIM: To compare the effectiveness of esomeprazole with the recommended dose of proton pump inhibitors in the healing of reflux oesophagitis, using omeprazole as a common comparator. METHODS: Systematic review of randomized controlled trials. Extraction and re-analysis of data to provide 'intention-to-treat' results. Meta-analysis using a Fixed Effects model. RESULTS: A meta-analysis of healing rates of esomeprazole 40 mg compared to omeprazole 20 mg gave the following results: at 4 weeks (relative risk 1.14; 95% CI: 1.10, 1.18) and 8 weeks (RR 1.08; 95%CI: 1.05, 1.10). Other proton pump inhibitors compared to omeprazole 20 mg are as follows: lansoprazole 30 mg at 4 weeks (RR 1.02; 95%CI: 0.97, 1.08) and 8 weeks (RR 1.01; 95%CI: 0.97, 1.06); pantoprazole 40 mg at 4 weeks (RR 0.99; 95%CI: 0.91, 1.07) and 8 weeks (RR 0.98; 95%CI: 0.93, 1.04); rabeprazole 20 mg at 4 weeks (RR 1.00; 95%CI: 0.87, 1.14) and 8 weeks (RR 0.98; 95%CI: 0.91, 1.05). CONCLUSIONS: Esomeprazole has demonstrated higher healing rates than omeprazole at 4 and 8 weeks. Other proton pump inhibitors (lansoprazole, pantoprazole and rabeprazole) have not shown higher healing rates when compared with omeprazole.     

Rabeprazole: a review of its use in acid-related gastrointestinal disorders.

Rabeprazole is an inhibitor of the gastric proton pump. It causes dose-dependent inhibition of acid secretion and has a more rapid onset of action than omeprazole. Duodenal ulcers healed faster after treatment with rabeprazole 20 or 40 mg/day than placebo or ranitidine 150 mg 4 times daily and at a generally similar rate to omeprazole 20 mg/day in patients with duodenal ulcers; rabeprazole was similar or superior to these agents in relieving symptoms. Rabeprazole 20 and 40 mg/day healed gastric ulcers faster than placebo, and rabeprazole 20 mg/day healed ulcers at a similar healing rate, to omeprazole 20 mg/day in well controlled 6-week studies. Gastric ulcer symptom relief with rabeprazole was similar or superior to that provided by omeprazole or placebo. In 8-week studies in patients with gastro-oesophageal reflux disease (GERD), rabeprazole 10, 20 and 40 mg/day were more effective than placebo, rabeprazole 20 mg/day was more effective than ranitidine 150 mg twice daily, and rabeprazole 20 mg/day was similar in efficacy to omeprazole 20 mg/day. Symptom relief with rabeprazole in 8-week trials in patients with GERD was superior to that provided by placebo, and similar to ranitidine or omeprazole. Rabeprazole was similar to omeprazole and superior to placebo in both maintenance of healing and prevention of symptoms in patients with healed GERD in 1-year studies. One-week triple therapy with rabeprazole 20 mg twice daily plus 2 antibacterial agents achieved > or = 90% Helicobacter pylori eradication, but, as would be expected, a regimen of rabeprazole 20 mg twice daily plus 1 antibacterial agent was less successful. The drug was as effective as omeprazole and lansoprazole as part of triple therapy for H. pylori eradication. Rabeprazole successfully reduced acid output to target levels and prevented further pathological changes in 10 patients with Zollinger-Ellison syndrome. Usual dosages of rabeprazole are 20 mg/day for 4 weeks to treat duodenal ulcers, 6 weeks for gastric ulcers and 8 weeks for GERD, although some patients with duodenal ulcer may respond to a 10 mg/day dosage. For long term maintenance of GERD healing, 10 or 20 mg daily doses are adequate. Patients with hypersecretory states may need individualised dosages starting at 60 mg/day. The drug was well tolerated in clinical trials, with headache, rash, infection, diarrhoea and flu syndrome as the most common adverse events. In conclusion, rabeprazole appears to be a well tolerated proton pump inhibitor with a rapid onset of action and a low potential for drug interactions. The drug may be used to achieve healing and the relief of symptoms of duodenal ulcer, gastric ulcer and GERD, maintain GERD healing, and can form part of effective regimens to eradicate H. pylori.     

Clinical trial: factors associated with freedom from relapse of heartburn in patients with healed reflux oesophagitis - results from the maintenance phase of the EXPO study

Background  A bility to predict freedom from heartburn relapse during maintenance therapy for healed reflux oesophagitis may facilitate optimal treatment choices for individual patients.
Aim  To determine factors predicting freedom from heartburn relapse during maintenance proton pump inhibitor therapy in patients with healed reflux oesophagitis.
Methods  This post-hoc analysis used data from the maintenance phase of the EXPO study (AstraZeneca study code: SH-NEG-0008); 2766 patients with healed reflux oesophagitis and resolved heartburn received once-daily esomeprazole 20 mg or pantoprazole 20 mg for 6 months. Multiple logistic regression analysis determined factors associated with freedom from heartburn relapse.
Results  Heartburn relapse rates were lower with esomeprazole than pantoprazole in all subgroups analysed. Esomeprazole treatment was the factor most strongly associated with freedom from heartburn relapse (odds ratio 2.08; P  <   0.0001). Other factors significantly associated with freedom from heartburn relapse were Helicobacter pylori infection, greater age, non-obesity, absence of epigastric pain at baseline, pre-treatment nonsevere heartburn and GERD symptom duration ≤5 years.
Conclusions  Several factors predict freedom from heartburn relapse during maintenance proton pump inhibitor therapy for healed reflux oesophagitis, the strongest being choice of proton pump inhibitor. These findings outline the importance of optimizing acid control and identifying predictors of relapse for effective long-term symptom management in reflux oesophagitis patients.