Authors: Baldwin, Claudine M.; Keam, Susan J.

Source: Drugs, Volume 69, Number 10, 9 July 2009 , pp. 1373-1401(29)

Publisher: Adis International

Abstract:

Abstract Rabeprazole (Aciphex®, Alfence®, Pariet®) is a proton pump inhibitor (PPI) used for the treatment of adults with conditions requiring a reduction of gastric acid secretion such as erosive or ulcerative gastro-oesophageal reflux disease (GORD), non-erosive reflux disease (NERD), duodenal and gastric ulcers, and pathological hypersecretory conditions including Zollinger-Ellison syndrome (ZES). It is also used as part of combination therapy for the eradication of Helicobacter pylori, a pathogen frequently implicated in the development of gastric and duodenal ulcers.

Rabeprazole has a well established efficacy and safety profile in the treatment of gastric acid-related diseases. Rabeprazole is a useful, well tolerated and cost-effective option for the treatment of GORD, NERD, peptic ulcer and other gastric acid-related diseases (including ZES), and provides an appropriate alternative to other currently available PPIs, with the added benefits of having a consistent efficacy profile and low drug interaction potential due to its predominantly nonenzymatic metabolism.

Pharmacological Properties Rabeprazole suppresses the secretion of gastric acid by noncompetitive blockade of the H+/K+-adenosine triphosphatase at the secretory surface of the gastric parietal cells. Rabeprazole demonstrated antisecretory activity, being more potent than lansoprazole, omeprazole and pantoprazole, but not esomeprazole during the first 24 hours after single doses in healthy volunteers and patients with GORD, but had less antisecretory activity than esomeprazole on days 1 and 5 after multiple doses in volunteers and patients with GORD. Mild gastric hyperplasia was seen in a minority of rabeprazole recipients, but there was no evidence of progression to high-grade hyperplasia in a 5-year study in patients with GORD. Rabeprazole has demonstrated good in vitro antibacterial activity against H. pylori.

Rabeprazole is rapidly absorbed, with peak plasma concentrations occurring ≈3.5 hours after administration. The oral bioavailability of rabeprazole is approximately 52% and its absorption is unaffected by food. Rabeprazole displayed dose-proportional pharmacokinetics over the dose range of 10-80 mg following single oral doses in healthy volunteers. The drug is widely distributed in a variety of tissues and is ≈97% protein bound. The metabolism of rabeprazole is predominantly via nonenzymatic reduction, and to a lesser extent via cytochrome P450 (CYP)2C19 and CYP3A4 isoenzymes. Rabeprazole is largely excreted via the urine, and the elimination half-life is ≈1 hour.

Rabeprazole may be safely utilized in the elderly, renally impaired and hepatically impaired, although caution is recommended when treating patients with severe liver disease.

Therapeutic Efficacy Rabeprazole was effective in the acute symptomatic treatment and healing of ulcerative or erosive GORD in well designed trials of 1 or 4-8 weeks' duration. There were no significant differences between rabeprazole 10-20 mg/day and omeprazole 20-40 mg/day in terms of symptom relief and oesophageal healing in patients with GORD. Over 80% of rabeprazole 20 mg/day or omeprazole 40 mg/day recipients had complete relief of heartburn symptoms by day 4 of treatment in one trial. In another trial, satisfactory heartburn relief was significantly faster, and a significantly greater proportion of patients had complete heartburn relief in each day of the first week of treatment with rabeprazole 20 mg/day compared with omeprazole 20 mg/day. CYP2C19 genotype did not affect healing rates at 4 and 8 weeks in one trial involving Japanese patients with erosive GORD. In longer-term trials, rabeprazole 10 or 20 mg once daily was effective in the prevention of GORD relapse and was an appropriate alternative to omeprazole 20 mg/day as maintenance therapy.

In Asian patients with NERD, rabeprazole 10 mg once daily provided as effective symptom relief as esomeprazole 20 mg once daily over a 4-week period.

Document Type: Research article

Affiliations: 1: Wolters Kluwer Health ∣ Adis, Auckland, New Zealand, an editorial office of Wolters Kluwer Health, Philadelphia, Pennsylvania, USA

Publication date: 2009-07-09

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