Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Rabeprazole: pharmacokinetics in patients with stable, compensated cirrhosis. 1036 34

Rabeprazole, a newly developed proton pump inhibitor, has been shown to be effective for the treatment of gastric and duodenal ulcers and for gastro-oesophageal reflux disease. It is a rapid and potent inhibitor of gastric H+,K(+)-ATPase, the gastric acid (proton) pump. The maximum plasma concentration (Cmax) and the area under the plasma concentration time curve (AUC) are linearly related to dose, while the time to maximum plasma concentration (tmax) and elimination half-life (t1/2) are dose-independent. Rabeprazole is extensively metabolized in the liver via the cytochrome P450 enzyme system, and its metabolites are excreted primarily in the urine. Rabeprazole does not accumulate with repeated dosing. Its bioavailability is not influenced by the coingestion of either food or antacids. The pharmacokinetic profile of rabeprazole is substantially altered in the elderly and patients with stable compensated chronic cirrhosis; however, these alterations are not associated with clinically significant abnormalities in laboratory parameters or serious adverse events. The influence of severe decompensated liver disease on the pharmacokinetics of rabeprazole has not been assessed. The pharmacokinetic profile of rabeprazole is not significantly altered by renal dysfunction requiring maintenance haemodialysis. These findings suggest that dosage adjustment is not required in these special patient populations. Caution should be exercised, however, in patients with severe liver disease.
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PMID:Review article: the pharmacokinetics of rabeprazole in health and disease. 1049 24