Related Experiment Videos
Spironolactone. I. Disposition and metabolism
Clinical Pharmacology and Therapeutics
|February 1, 1976
Summary
This study tracked the absorption, metabolism, and excretion of spironolactone (SP) in healthy men. The drug and its metabolite canrenone were largely protein-bound, with significant excretion via urine and feces over five days.
Area of Science:
- Pharmacokinetics
- Drug Metabolism
- Human Physiology
Background:
- Spironolactone (SP) is a medication used for various conditions.
- Understanding its absorption, distribution, metabolism, and excretion (ADME) is crucial for clinical application.
Purpose of the Study:
- To investigate the pharmacokinetic profile of spironolactone in healthy male subjects.
- To identify and quantify the major metabolites of spironolactone in humans.
Main Methods:
- Administration of a single oral dose of radiolabeled spironolactone ([20(-3)H]-SP) to 5 healthy men.
- Measurement of serum drug and metabolite levels over time.
- Analysis of urinary and fecal excretion of radioactivity and metabolites.
Main Results:
- Peak serum levels of extractable tritium and canrenone were observed within 3 hours.
- The elimination half-life of extractable tritium was approximately 37.3 hours.
- Major urinary metabolites included canrenone, 6beta-OH-sulfoxide, and canrenoate ester glucuronide; unchanged SP was not detected in urine.
Conclusions:
- Spironolactone undergoes extensive metabolism in humans, with canrenone being a primary metabolite.
- The drug and its metabolites exhibit high protein binding and are eliminated through both urine and feces.
- The pharmacokinetic data provide valuable insights into spironolactone's disposition in healthy individuals.