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Rabeprazole: pharmacokinetics in patients with stable, compensated cirrhosis
A M Hoyumpa1, H Trevino-Alanis, I Grimes
1Audie Murphy Veterans Administration Hospital, San Antonio, Texas, USA.
Clinical Therapeutics
|June 11, 1999
Summary
This study found that chronic liver disease significantly alters rabeprazole pharmacokinetics, increasing plasma concentrations in cirrhosis patients. However, rabeprazole (a proton-pump inhibitor) was well-tolerated in both healthy individuals and those with liver dysfunction.
Area of Science:
- Pharmacology
- Hepatology
- Drug Metabolism
Background:
- Proton-pump inhibitors (PPIs) are widely used for acid-related disorders.
- Understanding drug pharmacokinetics in liver disease is crucial for patient safety.
- Rabeprazole is a newer PPI with a distinct metabolic profile.
Purpose of the Study:
- To compare the tolerability and pharmacokinetics of rabeprazole in healthy volunteers versus patients with chronic cirrhosis.
- To assess the impact of liver dysfunction on rabeprazole absorption, distribution, metabolism, and excretion.
Main Methods:
- Single-center, open-label study involving 13 healthy males and 10 males with compensated cirrhosis.
- Administration of a single 20-mg oral dose of rabeprazole.
- Serial blood sampling for plasma rabeprazole concentration analysis via HPLC over 24 hours.
- Monitoring of adverse events, vital signs, ECGs, and laboratory parameters for tolerability assessment.
Main Results:
- Chronic liver disease significantly altered rabeprazole pharmacokinetics.
- Maximum plasma concentration was ~50% higher in cirrhosis patients (635 ng/mL) vs. healthy volunteers (401 ng/mL).
- Area under the curve and elimination half-life doubled in cirrhosis patients, while oral clearance decreased to 38% of that in healthy subjects.
- Rabeprazole was well-tolerated in both groups, with few clinically insignificant adverse events or laboratory changes.
Conclusions:
- Mild-to-moderate liver dysfunction markedly reduces rabeprazole clearance and increases plasma levels.
- Despite pharmacokinetic alterations, rabeprazole 20 mg once daily is unlikely to cause drug accumulation in patients with mild-to-moderate liver dysfunction.
- Dose adjustment for rabeprazole does not appear necessary in patients with mild-to-moderate liver dysfunction, though caution is advised in severe liver disease.