Review article: pharmacokinetic concerns in the selection of anti-ulcer therapy

Abstract

Rabeprazole is a new, highly potent proton pump inhibitor (PPI) being introduced for the treatment of disorders of gastric acid hypersecretion. Rabeprazole joins other drugs in this class, such as omeprazole, pantoprazole, and lansoprazole, which share a common mechanism of action. Each of these drugs is a substituted benzimidazole, which inhibits activity of the H+, K+ -ATPase located on the apical surface of parietal cells, thereby preventing the secretion of gastric acid. As a result of structural and functional similarities, the PPIs share many pharmacokinetic features. They have comparable rates of absorption, maximum plasma concentrations, and total drug absorptions resulting in similar bioavailability after single-dose administration. With multiple dosing, rabeprazole differs from omeprazole in that its pharmacokinetic profile does not change significantly over the course of therapy. All the PPIs are metabolized rapidly, resulting in short half-lives. However, their duration of activity is much longer, due to the way in which they bind to H+, K+ -ATPase. All are metabolized by hepatic cytochrome P450 enzymes, although only omeprazole has demonstrated significant interactions with other drugs metabolized by this pathway. Rabeprazole, which has a low potential for interacting with drugs metabolized by cytochrome P450, does interfere with the absorption of digoxin and ketoconazole because of its antisecretory effects. The pharmacokinetics of rabeprazole are altered slightly in elderly subjects and in patients with renal and moderate hepatic disease. However, the pharmacokinetic findings suggest that no dosage adjustment is required in these special populations.