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| Other names | 7α-TMS; SC-26519; 17α-Hydroxy-7α-(methylthio)-3-oxopregn-4-ene-21-carboxylic acid γ-lactone |
| Drug class | Antimineralocorticoid |
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| Formula | C23H32O3S |
| Molar mass | 388.57 g·mol−1 |
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7α-Thiomethylspironolactone (7α-TMS; developmental code name SC-26519) is a steroidal antimineralocorticoid and antiandrogen of the spirolactone group and the major active metabolite of spironolactone.[1] Other important metabolites of spironolactone include 7α-thiospironolactone (7α-TS; SC-24813), 6β-hydroxy-7α-thiomethylspironolactone (6β-OH-7α-TMS), and canrenone (SC-9376).[2][3][1][4]
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]
7α-TS and 7α-TMS have been found to possess approximately equivalent affinity for the rat ventral prostate androgen receptor (AR) relative to that of spironolactone.[8] The affinity of 7α-TS, 7α-TMS, and spironolactone for the rat prostate AR is about 3.0 to 8.5% of that of dihydrotestosterone (DHT).[8]
| Compound | Cmax (day 1) | Cmax (day 15) | AUC (day 15) | t1/2 |
|---|---|---|---|---|
| Spironolactone | 72 ng/mL (173 nmol/L) | 80 ng/mL (192 nmol/L) | 231 ng•hour/mL (555 nmol•hour/L) | 1.4 hours |
| Canrenone | 155 ng/mL (455 nmol/L) | 181 ng/mL (532 nmol/L) | 2,173 ng•hour/mL (6,382 nmol•hour/L) | 16.5 hours |
| 7α-TMS | 359 ng/mL (924 nmol/L) | 391 ng/mL (1,006 nmol/L) | 2,804 ng•hour/mL (7,216 nmol•hour/L) | 13.8 hours |
| 6β-OH-7α-TMS | 101 ng/mL (250 nmol/L) | 125 ng/mL (309 nmol/L) | 1,727 ng•hour/mL (4,269 nmol•hour/L) | 15.0 hours |
| Sources: See template. | ||||
7α-TMS has been found to account for around 80% of the potassium-sparing effect of spironolactone,[6][9][10] whereas canrenone accounts for the remaining approximate 10 to 25% of the potassium-sparing effect of the drug.[11]
See also
References
Further reading
- Gardiner P, Schrode K, Quinlan D, Martin BK, Boreham DR, Rogers MS, et al. (April 1989). "Spironolactone metabolism: steady-state serum levels of the sulfur-containing metabolites". Journal of Clinical Pharmacology. 29 (4): 342–347. doi:10.1002/j.1552-4604.1989.tb03339.x. PMID 2723123. S2CID 29457093.