Canrenone
Chemical compound
From Wikipedia, the free encyclopedia
Canrenone, sold under the brand names Contaren, Luvion, Phanurane, and Spiroletan, is a steroidal antimineralocorticoid[3][4] of the spirolactone group related to spironolactone which is used as a diuretic in Europe, including Italy and Belgium.[5][6][7][8] It is also an important active metabolite of spironolactone, and partially accounts for its therapeutic effects.[9][2]
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| Trade names | Contaren, Luvion, Phanurane, Spiroletan |
| Other names | Aldadiene;[1] SC-9376; RP-11614; 7α-Desthioacetyl-δ6-spironolactone; 6,7-Dehydro-7α-desthioacetylspironolactone; 17-Hydroxy-3-oxo-17α-pregna-4,6-diene-21-carboxylic acid γ-lactone |
| AHFS/Drugs.com | International Drug Names |
| Drug class | Antimineralocorticoid |
| ATC code | |
| Pharmacokinetic data | |
| Protein binding | 95% |
| Elimination half-life | 16.5 hours[2] |
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| ECHA InfoCard | 100.012.322 |
| Chemical and physical data | |
| Formula | C22H28O3 |
| Molar mass | 340.463 g·mol−1 |
| 3D model (JSmol) | |
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Medical uses
Two studies of canrenone in people with heart failure have shown a benefit compared to placebo. In an evaluation of people with chronic heart failure (CHF), [10]
One study compared 166 people treated with canrenone to 336 people given conventional therapy, both for 10 years. Overall, people that were treated with canrenone displayed a lower number of deaths and longer survival compared to the placebo group. Patients treated with canrenone had lower systolic and diastolic blood pressure compared to conventional therapy. Uric acid was lower in the group treated with canrenone, as was left ventricular mass, and a greater progression of NYHA class was observed in the control group compared to patients treated with canrenone. However, no differences were seen in potassium, sodium, and brain natriuretic peptide (BNP) levels.[10]
A separate study concluded that treatment with canrenone, alongside optimal therapy, in patients with chronic heart failure improved diastolic function and further decreased BNP levels.[11]
Canrenone has also been found to be effective in the treatment of hirsutism in women.[12]
Pharmacology
Pharmacodynamics
Canrenone is reportedly more potent as an antimineralocorticoid relative to spironolactone, but is considerably less potent and effective as an antiandrogen.[13][14] Similarly to spironolactone, canrenone inhibits steroidogenic enzymes such as 11β-hydroxylase, cholesterol side-chain cleavage enzyme, 17α-hydroxylase, 17,20-lyase, and 21-hydroxylase but is comparatively less potent in doing so.[15]
Pharmacokinetics
The elimination half-life of canrenone is about 16.5 hours.[2]
As a metabolite
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), accounts for around 80% of the potassium-sparing effect of the drug.[17][18][19]
| 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. | ||||
History
Canrenone was described and characterized in 1959.[5] It was introduced for medical use, in the form of potassium canrenoate (the potassium salt of canrenoic acid), in 1968.[20]