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Related Experiment Video

Updated: Apr 7, 2026

Invasive Hemodynamic Characterization of the Portal-hypertensive Syndrome in Cirrhotic Rats

Invasive Hemodynamic Characterization of the Portal-hypertensive Syndrome in Cirrhotic Rats

Published on: August 1, 2018

Spironolactone pharmacokinetics and pharmacodynamics in patients with cirrhotic ascites.

I Sungaila¹, W R Bartle, S E Walker

¹Department of Pharmacy, Sunnybrook Health Science Centre, Toronto, Ontario.

Gastroenterology

|May 1, 1992

Summary

Spironolactone (SP) metabolism is impaired in patients with cirrhosis, leading to longer half-lives for SP and its metabolites. This impacts drug clearance and requires further investigation in this population.

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Published on: December 3, 2020

Area of Science:

Pharmacology
Hepatology
Clinical Chemistry

Background:

Spironolactone (SP) is a medication used to treat conditions like ascites.
Understanding its metabolism in liver disease is crucial for effective treatment.
Cirrhosis can significantly alter drug pharmacokinetics.

Purpose of the Study:

To determine the pharmacokinetic and pharmacodynamic properties of spironolactone (SP) and its metabolites in patients with cirrhosis.
To assess the impact of cirrhosis on the elimination and concentration of SP and its active metabolites.
To investigate the relationship between drug clearance and therapeutic effects in cirrhotic patients.

Main Methods:

A study involving nine patients with cirrhosis and ascites.
Serial blood and urine samples collected over 26 hours.
Analysis of SP and metabolites (canrenone, 6 beta-hydroxy-7 alpha-thiomethylspirolactone, 7 alpha-thiomethylspirolactone) using high-performance liquid chromatography (HPLC).

Main Results:

Increased terminal half-lives were observed for SP and its metabolites compared to normal individuals.
The apparent half-lives were 9.04 hours for SP, 126 hours for 6 beta-hydroxy-7 alpha-thiomethylspirolactone, 23.9 hours for 7 alpha-thiomethylspirolactone, and 57.8 hours for canrenone.
Clearance-effect relationships were most strongly correlated with 7 alpha-thiomethylspirolactone and canrenone.

Conclusions:

Spironolactone metabolism is impaired in patients with cirrhosis.
The prolonged half-lives suggest altered drug processing in this patient group.
Further research is needed to fully characterize SP pharmacokinetics and pharmacodynamics in cirrhosis.