Review article: the pharmacokinetics of rabeprazole in health and disease

Rabeprazole, a newly developed proton pump inhibitor, has been shown to be effective for the treatment of gastric and duodenal ulcers and for gastro-o esophageal reflux disease. It is a rapid and potent inhibitor of gastric H,K+-ATPase, the gastric acid (proton) pump. The maximum plasma concentratio n (C-max) and the area under the plasma concentration time curve (AUC) are linearly related to dose, while the time to maximum plasma concentration (t (max)) and elimination half-life (t(1/2)) are dose-independent. Rabeprazole is extensively metabolized in the liver via the cytochrome P450 enzyme sys tem, and its metabolites are excreted primarily in the urine. Rabeprazole d oes not accumulate with repeated dosing. Its bioavailability is not influen ced by the coingestion of either food or antacids. The pharmacokinetic prof ile of rabeprazole is substantially altered ire the elderly and patients wi th stable compensated chronic cirrhosis; however, these alterations are not associated with clinically significant abnormalities in laboratory paramet ers or serious adverse events. The influence of severe decompensated liver disease on the pharmacokinetics of rabeprazole has not been assessed. The p harmacokinetic profile of rabeprazole is not significantly altered by renal dysfunction requiring maintenance haemodialysis. These findings suggest th at dosage adjustment is not required in these special patient populations. Caution should be exercised, however, in patients with severe liver disease .