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Pharmacokinetics of 100 mg/day spironolactone and its metabolites Compound C max Tooltip Peak concentrations (day 1) C max Tooltip Peak concentrations (day 15) AUC Tooltip Area-under-the-curve concentrations (day 15) t 1/2 Tooltip Elimination half-life; Spironolactone: 72 ng/mL (173 nmol/L) 80 ng/mL (192 nmol/L) 231 ng•hour/mL (555 nmol ...
Spironolactone has been identified as an inhibitor of NRG1‐ERBB4 signaling. [142] Spironolactone has been found to act as a potent inhibitor of the pannexin 1 channel, and this action appears to be involved in its antihypertensive effects independently of MR antagonism. [143] Spironolactone has been found to block hERG channels. [144]
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However, spironolactone is metabolized to three active metabolites, which give it prolonged activity (13.8 – 16. 5 hours). Spironolactone has a long half-life and is excreted 47-51% through kidneys. Patients with chronic kidney disease therefore require close monitoring when taking the drug. Spironolactone is also eliminated through feces (35-41%
[11] [185] [186] Other known but more minor metabolites of spironolactone include 7α-thiospironolactone (7α-TS), which is an important intermediate to the major metabolites of spironolactone, [17] as well as the 7α-methyl ethyl ester of spironolactone and the 6β-hydroxy-7α-methyl ethyl ester of spironolactone.
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Spironolactone is a prodrug with a short terminal half-life of 1.4 hours. [5] [6] [7] The active metabolites of spironolactone have extended terminal half-lives of 13.8 hours for 7α-TMS, 15.0 hours for 6β-OH-7α-TMS, and 16.5 hours for canrenone, and accordingly, these metabolites are responsible for the therapeutic effects of the drug. [5] [6
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