Rabeprazole: Pharmacokinetics in patients with stable, compensated cirrhosis

• Published in: Clinical therapeutics Vol. 21; no. 4; pp. 691 - 701
• Main Authors: Hoyumpa, Anastacio M., Trevino-Alanis, Hector, Grimes, Imogene, Humphries, Thomas J.
• Format: Journal Article
• Language: English
• Published: Belle Mead, NJ EM Inc USA 01.04.1999; Excerpta Medica
• Subjects: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Benzimidazoles - pharmacokinetics; Benzimidazoles - therapeutic use; Biological and medical sciences; Chronic Disease; cirrhosis; Digestive system; Enzyme Inhibitors - pharmacokinetics; Enzyme Inhibitors - therapeutic use; Humans; Liver Cirrhosis - drug therapy; Male; Medical sciences; Middle Aged; Omeprazole - analogs & derivatives; Pharmacology. Drug treatments; proton-pump inhibitors; Proton-Translocating ATPases - antagonists & inhibitors; Rabeprazole; Single-Blind Method; proton-pump inhibitors; rabeprazole; cirrhosis; Human; Cirrhosis; Benzimidazole derivatives; Toxicity; Single dose; Oral administration; Digestive diseases; Hepatic disease; Rabeprazole; Pharmacokinetics; Proton pump inhibitor
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/S0149-2918(00)88320-4

This single-center, open-label study was undertaken to compare the tolerability and pharmacokinetic profiles of rabeprazole, a new proton-pump inhibitor (PPI), in healthy volunteers and in subjects with chronic cirrhosis. Thirteen healthy men and 10 men with stable, compensated cirrhosis documented by biopsy or liver/ spleen scan received a single 20-mg rabeprazole dose. Blood samples were drawn before and up to 24 hours after drug administration for the determination of plasma rabeprazole concentrations using high-performance liquid chromatography. Adverse events, vital signs, electrocardiograms, physical findings, and clinical laboratory test results were monitored before and during treatment to determine how rabeprazole was tolerated. Chronic liver disease substantially altered the pharmacokinetic profile of rabeprazole. The maximum rabeprazole concentration (± SD) in subjects with cirrhosis (635 ±199 ng/mL) was approximately 50% higher than that in the healthy volunteers (401 ± 246 ng/mL), and both area under the curve and elimination half-life were increased by approximately 100%. Oral clearance in subjects with cirrhosis was 38% of that in the healthy volunteers. Rabeprazole was well tolerated by both groups. Three subjects reported a total of 5 clinical adverse events that were judged as definitely or possibly related to rabeprazole treatment. Some minor changes in laboratory values were judged to be clinically insignificant. In patients with mild-to-moderate liver dysfunction, clearance of this PPI, as with other members of the class, was markedly reduced and plasma levels were increased. Although caution is always warranted in patients with severe liver disease, drug accumulation is unlikely with rabeprazole 20 mg once daily, and dose adjustment does not appear to be indicated in patients with mild-to-moderate liver dysfunction.