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They are common during spironolactone therapy, with 10 to 50% of women experiencing them at moderate doses and almost all experiencing them at a high doses. [86] [111] For example, about 20% of women experienced menstrual irregularities with 50 to 100 mg/day spironolactone, whereas about 70% experienced menstrual irregularities at 200 mg/day. [63]
However, the dosages of spironolactone used in animals to produce progestogenic effects were very high (50–200 mg/kg/day in rabbits, 400 mg/day in rhesus monkeys). [118] In one study, the threshold dose by subcutaneous injection for endometrial transformation in rabbits was 0.003–0.01 mg for cyproterone acetate , 0.1–0.3 mg for ...
The objective of this trial was to assess the impact of spironolactone on morbidity and mortality in patients with severe heart failure. Patients were randomized to receive either spironolactone (25 to 50 mg) daily or placebo. Both groups were continued on standard therapy. The primary endpoint was all-cause mortality.
Eplerenone differs from spironolactone in its extensive metabolism, with a short half-life and inactive metabolites. [4] Eplerenone seems to be about 50 to 75% as potent as spironolactone as an antimineralocorticoid. [24] Hence, 25 mg/day spironolactone may be equivalent to approximately 50 mg/day eplerenone. [25]
Spirolactones are a class of functional group in organic chemistry featuring a cyclic ester attached spiro to another ring system. The name is also used to refer to a class of synthetic steroids, called steroid-17α-spirolactones, 17α-spirolactosteroids, or simply 17α-spirolactones, which feature their spirolactone group at the C17α position.
Canrenone is an active metabolite of spironolactone, canrenoic acid, and potassium canrenoate, and is considered to be partially responsible for their effects. [9] It has been found to have approximately 10 to 25% of the potassium-sparing diuretic effect of spironolactone, [ 16 ] whereas another metabolite, 7α-thiomethylspironolactone (7α-TMS ...
For comparison to progesterone, a 200 mg dose of oral progesterone is considered to be approximately equivalent in antimineralocorticoid effect to a 25 to 50 mg dose of spironolactone. [88] Both drospirenone and progesterone are actually weak partial agonists of the MR in the absence of mineralocorticoids. [6] [5] [66]
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]