Biological Half-Life of Spironolactone
Spironolactone has a short half-life of approximately 1.4 hours, but its active metabolites have much longer half-lives ranging from 13.8 to 16.5 hours, which accounts for its prolonged clinical effects. 1
Pharmacokinetics of Spironolactone
Parent Compound
- Spironolactone itself has a mean half-life of only 1.4 hours 1
- Peak plasma concentration is reached in approximately 2.6 hours 1
- Food increases bioavailability by approximately 95.4% 1
- Protein binding exceeds 90% 1
Active Metabolites
Spironolactone undergoes extensive metabolism to several active metabolites with significantly longer half-lives:
- Canrenone: 16.5 hours 1, 2
- 7-α-(thiomethyl) spironolactone (TMS): 13.8 hours 1, 2
- 6-ß-hydroxy-7-α-(thiomethyl) spironolactone (HTMS): 15 hours 1
Clinical Implications of Spironolactone's Half-Life
Dosing Considerations
- Despite the short half-life of the parent compound, the long half-life of the active metabolites allows for once-daily dosing in most clinical scenarios 3
- Steady-state concentrations require 3-4 days to achieve due to the accumulation of active metabolites 3
- When initiating therapy, the full clinical effect may be delayed for several days due to this pharmacokinetic profile 3
Comparison to Other Aldosterone Antagonists
- Eplerenone has a shorter half-life than spironolactone's metabolites and does not produce active metabolites 4
- This pharmacokinetic difference contributes to the lower incidence of hyperkalemia with eplerenone compared to spironolactone 4
Special Populations
- The terminal half-life of spironolactone may be increased in patients with cirrhotic ascites 1
- In infants and young children, the pharmacokinetics of spironolactone and its metabolites show high variability, with body weight explaining about 22% of this variability 5
Elimination
- Metabolites are primarily excreted in the urine and secondarily in bile 1
- After oral administration, approximately 31.6% of the drug is excreted in urine and 22.7% in feces over 5 days 6
The prolonged clinical effect of spironolactone, despite its short parent compound half-life, is due to the extended half-lives of its active metabolites. This explains why spironolactone can be effectively administered once daily despite the parent compound's rapid elimination.