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Xipamide disposition in liver cirrhosis
H Knauf1, W Gerok, E Mutschler
1Medizinische Universitätsklinik, Freiburg, Germany.
Clinical Pharmacology and Therapeutics
|December 1, 1990
Summary
The pharmacokinetics of xipamide, a diuretic, were altered in liver cirrhosis patients. Reduced nonrenal clearance, linked to cholestasis, increased drug levels and urine excretion.
Area of Science:
- Pharmacology
- Hepatology
- Clinical Pharmacy
Background:
- Liver cirrhosis and ascites significantly alter drug pharmacokinetics.
- Sulfonamide diuretics like xipamide are used to manage fluid retention in these patients.
- Understanding xipamide's behavior in cirrhosis is crucial for safe and effective treatment.
Purpose of the Study:
- To investigate the pharmacokinetics of xipamide in patients with liver cirrhosis and ascites.
- To compare xipamide's absorption, distribution, and excretion in cirrhotic patients versus healthy controls.
- To identify factors influencing xipamide's disposition in liver disease.
Main Methods:
- Oral administration of 40 mg xipamide to cirrhotic patients and healthy controls.
- Measurement of plasma and ascitic fluid concentrations over time.
- Analysis of the area under the concentration-time curve (AUC) and urinary excretion (Ae).
- Correlation analysis with plasma direct bilirubin levels.
Main Results:
- Xipamide rapidly distributed into plasma and ascitic fluid.
- Plasma AUC of xipamide was significantly higher in cirrhotic patients (p < 0.001).
- Urinary excretion of parent drug and metabolite (Ae) was significantly increased (p < 0.001).
- Renal clearance was only moderately reduced; AUC and Ae correlated with direct bilirubin (p < 0.05).
Conclusions:
- Nonrenal clearance of xipamide is reduced in liver cirrhosis.
- This reduction is attributed to impaired hepatobiliary excretion during cholestasis.
- Altered pharmacokinetics necessitate careful consideration in cirrhotic patients.