Rabeprazole

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Abstract
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 ≥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 H2 antagonists and an additional treatment option to other proton pump inhibitors in the management of acid-related disorders. Rabeprazole inhibits the gastric parietal cell proton pump (H+/K+-ATPase), dose-dependently reducing basal and peptone-stimulated acid secretion with 20 mg/day providing the optimum antisecretory effect. In healthy volunteers, rabeprazole had a similar or faster onset of action than omeprazole and pantoprazole. In addition, rabeprazole had a greater antisecretory effect over a 24-hour period than esomeprazole, omeprazole, lansoprazole and pantoprazole. Rabeprazole had a duration of action of ≥24 hours. Among patients with gastro-oesophageal reflux disease (GORD) rabeprazole is as effective as omeprazole and more effective than placebo in normalising 24-hour oesophageal acid exposure. Rabeprazole produces dose-dependent increases in gastrin levels which are directly related to increases in pH and has no effect on endocrine function. Unlike omeprazole and lansoprazole, multiple-dose studies in volunteers have shown the effect of rabeprazole on intragastric pH to be unaffected by cytochrome P450 (CYP) 2C19 genotype status. Rabeprazole is dose-dependently absorbed after oral administration and is extensively metabolised primarily via nonenzymatic metabolism with minor contributions from CYP 3A and 2C19 pathways. Rabeprazole is extensively distributed in a variety of tissues including gastric mucosa and 96% bound to plasma proteins. No significant accumulation occurs during repeated administration, and 90% of a dose is excreted in the urine as its thioether carboxylic acid metabolite and its glucuronide and mercapturic acid metabolites. The elimination half-life of rabeprazole is ≈1 to 2 hours. Other than pH-dependent interactions with digoxin and ketoconazole, rabeprazole has no clinically significant drug interactions. Administration of food slows the rate but does not affect the extent of absorption. The efficacy of oral rabeprazole has been studied in patients with gastric or duodenal ulcers, erosive and nonerosive GORD, Zollinger-Ellison syndrome and Helicobacter pylori infection. GORD. Rabeprazole 20 mg/day was as effective as omeprazole 20 mg/day and superior to ranitidine 150mg four times daily in the healing of erosive GORD. In addition, the proportion of patients who reported improvement in the frequency of heartburn, complete resolution of daytime heartburn severity, complete resolution of night-time heartburn severity and overall well-being were significantly higher in rabeprazole-treated patients than in those receiving ranitidine. Preliminary data from two 1-week, well designed trials comparing rabeprazole 20 mg/day with omeprazole 20 or 40 mg/day in patients with erosive GORD suggest rabeprazole may provide faster resolution of symptoms than omeprazole. Well designed trials have compared the efficacy of rabeprazole 10 and 20 mg/day with placebo or omeprazole 20 mg/day in maintaining healing and symptom relief in patients following healing of grades 2 to 4 GORD. One study demonstrated no difference in relapse rates between rabeprazole 10 mg/day and omeprazole 20 mg/day regimens after 1 year of treatment. In addition, the probability of remaining healed at 2 years was 100% for patients treated with omeprazole 20 mg/day or rabeprazole 10...