Rabeprazole: Pharmacokinetics and tolerability in patients with stable, end-stage renal failure

The authors compare the pharmacokinetic profiles, safety, and tolerability of rabeprazole, a new proton pump inhibitor (PPI), in healthy volunteers an d in subjects with stable, endstage renal failure. This single-center open- label trial included two groups of subjects: 10 healthy males with 24-hour creatinine clearance greater than or equal to 90 mL/min/m(2) and 10 males w ith renal failure (24-hour creatinine clearance less than or equal to 5 mL/ min/m(2)) receiving hemodialytic therapy. Normal subjects received a single , oral 20 mg rabeprazole dose. Those with renal failure received a 20 mg do se of rabeprazole on the day after hemodialysis and a second dose after a a -week washout period during dialysis. Blood samples were drawn before and u p to 24 hours after rabeprazole administration for determination of plasma rabeprazole concentrations by high-performance liquid chromatography. Safet y and tolerability of rabeprazole were determined by reporting adverse even ts and comparing vital signs, EGG, physical examinations, and clinical labo ratory tests before and during treatment. Comparison of pharmacokinetic res ults from healthy volunteers with those from subjects with renal failure in dicated no clinically significant differences between groups. In addition, there were no statistically significant differences between any pharmacokin etic parameters recorded during or after hemodialysis. Rabeprazole was well tolerated by both groups. Only two drug-related adverse events were report ed, and there were no significant treatment-emergent changes in vital signs or EGG. Treatment-emergent changes in hematologic and clinical chemistry p arameters were observed for a few subjects in each group and generally repr esented only slight deviations from the normal range. These results indicat e that no dosage adjustment of rabeprazole is required in patients with ren al dysfunction. These findings and the well-documented clinical efficacy of this new PPI in patients with gastric ulcers, duodenal ulcers, or gastroes ophageal reflux disease support rabeprazole's use in the treatment of patie nts with acid peptic disorders. Journal of Clinical pharmacology, 1999;39:9 27-933 (C) 1999 the American College of Clinical Pharmacology.