Canrenone

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 in 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]

Canrenone

Clinical data
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	C03DA03 (WHO)
Pharmacokinetic data
Protein binding	95%
Elimination half-life	16.5 hours[2]
Identifiers
IUPAC name 10,13-Dimethylspiro[2,8,9,11,12,14,15,16-octahydro-1H-cyclopenta[a]phenanthrene-17,5'-oxolane]-2',3-dione
CAS Number	976-71-6 N
PubChem CID	13789
ChemSpider	13192 Y
UNII	78O20X9J0U
ChEMBL	ChEMBL1463345 N
CompTox Dashboard (EPA)	DTXSID3045930
ECHA InfoCard	100.012.322
Chemical and physical data
Formula	C22H28O3
Molar mass	340.463 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C5\C=C4\C=C/[C@@H]1[C@H](CC[C@]3([C@H]1CC[C@]32OC(=O)CC2)C)[C@@]4(C)CC5
InChI InChI=1S/C22H28O3/c1-20-9-5-15(23)13-14(20)3-4-16-17(20)6-10-21(2)18(16)7-11-22(21)12-8-19(24)25-22/h3-4,13,16-18H,5-12H2,1-2H3/t16-,17+,18+,20+,21+,22-/m1/s1 Y Key:UJVLDDZCTMKXJK-WNHSNXHDSA-N Y
NY (what is this?)  (verify)

Medical uses

Canrenone has been found to be effective in the treatment of hirsutism in women.^[10]

Heart failure

Two studies of canrenone in people with heart failure have shown a mortality benefit compared to placebo. In the evaluation which studied people with chronic heart failure (CHF), people that were treated with canrenone displayed a lower number of deaths compared to the placebo group, indicating a death and morbidity benefit of the medication.

One study compared 166 treated with canrenone to 336 given conventional therapy lasting 10 years. Differences in systolic and diastolic blood pressure was observed between both patient groups where, patients treated with canrenone, showed a lower blood pressure compared to conventional therapy. Uric acid was lower in the group treated with canrenone; however, no differences were seen in potassium, sodium, and brain natriuretic peptide (BNP) levels. Left ventricular mass was also lower in the group treated with canrenone and a greater progression of NYHA class was observed in the control group compared to patients treated with canrenone.^[11]

Another study concluded that treatment with canrenone in patients with chronic heart failure improves diastolic function and further decreased BNP levels.^[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 once again, 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]

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Pharmacokinetics of 100 mg/day spironolactone and its metabolites

Compound	CmaxTooltip Peak concentrations (day 1)	CmaxTooltip Peak concentrations (day 15)	AUCTooltip Area-under-the-curve concentrations (day 15)	t1/2Tooltip Elimination half-life
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-TMSTooltip 7α-Thiomethylspironolactone	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-TMSTooltip 6β-Hydroxy-7α-thiomethylspironolactone	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), by 1968.^[20]

Society and culture

Generic names

Canrenone is the INNTooltip International Nonproprietary Name and USANTooltip United States Adopted Name of the drug.^[6][8]

Brand names

Canrenone has been marketed under the brand names Contaren, Luvion, Phanurane, and Spiroletan, among others.^[5][8][20]

Availability

Canrenone appears to remain available only in Italy, although potassium canrenoate remains marketed in various other countries as well.^[21][22]

See also

• Canrenoic acid
• Potassium canrenoate