Furosemide disposition in cirrhosis

Area of Science:

• Pharmacokinetics
• Clinical Pharmacology
• Drug Metabolism

Background:

• Cirrhosis and ascites can alter drug disposition.
• Understanding furosemide pharmacokinetics is crucial for managing fluid overload in these patients.

Purpose of the Study:

• To investigate furosemide disposition in patients with cirrhosis and ascites compared to healthy subjects.
• To determine if altered drug disposition contributes to changes in furosemide efficacy.

Main Methods:

• Administered intravenous furosemide (80 mg) to 10 healthy subjects and 8 cirrhotic patients.
• Measured plasma concentrations and urinary excretion of furosemide and its metabolite.
• Calculated pharmacokinetic parameters including half-life, clearance, and volume of distribution.

Main Results:

• Furosemide elimination half-life was longer in cirrhotic patients (81.0 min) versus healthy subjects (60.2 min).
• Systemic clearance remained similar, but the volume of distribution increased in cirrhotic patients.
• Increased unbound furosemide in plasma of cirrhotic patients correlated with distribution changes.
• Urinary recovery of unchanged furosemide and its glucuronide metabolite was comparable between groups.

Conclusions:

• Cirrhosis modestly affects furosemide disposition, primarily through altered distribution, not clearance.
• Changes in furosemide diuretic efficacy in cirrhosis are likely due to altered pharmacodynamic factors, not disposition.