Chemical compound
Canrenone
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
Protein binding 95%
Elimination half-life 16.5 hours
[2]
10,13-Dimethylspiro[2,8,9,11,12,14,15,16-octahydro-1H -cyclopenta[a ]phenanthrene-17,5'-oxolane]-2',3-dione
CAS Number
PubChem
CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (
EPA )
ECHA InfoCard
100.012.322
Formula C 22 H 28 O 3
Molar mass 340.463 g·mol−1 3D model (
JSmol )
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=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
N Y
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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]
Medical uses
Canrenone is mainly used as a
diuretic .[
citation needed ]
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]
Pharmacokinetics of 100 mg/day spironolactone and its metabolites
Compound
Cmax Tooltip Peak concentrations (day 1)
Cmax Tooltip Peak concentrations (day 15)
AUC Tooltip Area-under-the-curve concentrations (day 15)
t1/2 Tooltip 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-TMS Tooltip 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-TMS Tooltip 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
INN Tooltip International Nonproprietary Name and
USAN Tooltip 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
References
^ Müller J (6 December 2012).
Regulation of Aldosterone Biosynthesis: Physiological and Clinical Aspects . Springer Science & Business Media. pp. 164–.
ISBN
978-3-642-83120-1 .
^
a
b
c 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 .
^ Losert W, Casals-Stenzel J, Buse M (1985). "Progestogens with antimineralocorticoid activity". Arzneimittel-Forschung . 35 (2): 459–471.
PMID
4039568 .
^ Fernandez MD, Carter GD, Palmer TN (January 1983).
"The interaction of canrenone with oestrogen and progesterone receptors in human uterine cytosol" . British Journal of Clinical Pharmacology . 15 (1): 95–101.
doi :
10.1111/j.1365-2125.1983.tb01470.x .
PMC
1427833 .
PMID
6849751 .
^
a
b
c Elks J (14 November 2014).
The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies . Springer. pp. 210–.
ISBN
978-1-4757-2085-3 .
^
a
b Hill R, Makin H, Kirk D, Murphy G (23 May 1991).
Dictionary of Steroids . CRC Press. pp. 656–.
ISBN
978-0-412-27060-4 .
^ Romanelli RG, Gentilini P (May 2004).
"Cross reactivity due to positive canrenone interference" . Gut . 53 (5): 772–773.
PMC
1774040 .
PMID
15082604 .
^
a
b
c
Index Nominum 2000: International Drug Directory . Taylor & Francis. January 2000. pp. 167–.
ISBN
978-3-88763-075-1 .
^
a
b Clark MA, Harvey RA, Finkel R, Rey JA, Whalen K (15 December 2011).
Pharmacology . Lippincott Williams & Wilkins. pp. 286–.
ISBN
978-1-4511-1314-3 .
^ Sobbrio GA, Granata A, Panacea A, Trimarchi F (1989). "Effectiveness of short term canrenone treatment in idiopathic hirsutism". Minerva Endocrinologica . 14 (2): 105–108.
PMID
2761494 .
^ Derosa G, Maffioli P, Scelsi L, Bestetti A, Vanasia M, Cicero AF, et al. (March 2019). "Canrenone on cardiovascular mortality in congestive heart failure: CanrenOne eFFects on cardiovascular mortality in patiEnts with congEstIve hearT failure: The COFFEE-IT study". Pharmacological Research . 141 : 46–52.
doi :
10.1016/j.phrs.2018.11.037 .
PMID
30502530 .
S2CID
54564252 .
^ de Simone G, Chinali M, Mureddu GF, Cacciatore G, Lucci D, Latini R, et al. (October 2011). "Effect of canrenone on left ventricular mechanics in patients with mild systolic heart failure and metabolic syndrome: the AREA-in-CHF study". Nutrition, Metabolism, and Cardiovascular Diseases . 21 (10): 783–791.
doi :
10.1016/j.numecd.2010.02.012 .
PMID
21939839 .
^ Coelingh Benni H, Vemer H (15 December 1990).
Chronic Hyperandrogenic Anovulation . CRC Press. pp. 152–.
ISBN
978-1-85070-322-8 .
^ Seldin DW, Giebisch GH (23 September 1997).
Diuretic Agents: Clinical Physiology and Pharmacology . Academic Press. pp. 630–.
ISBN
978-0-08-053046-8 .
^ Colby HD (April 1981).
"Chemical suppression of steroidogenesis" . Environmental Health Perspectives . 38 : 119–127.
doi :
10.1289/ehp.8138119 .
PMC
1568425 .
PMID
6786868 .
^ Angeli P, Gatta A (15 April 2008).
"Medical Treatment of Ascites in Cirrhosis" . In Ginés P, Arroyo V, Rodés J, Schrier RW (eds.).
Ascites and Renal Dysfunction in Liver Disease: Pathogenesis, Diagnosis, and Treatment . John Wiley & Sons. p. 229.
ISBN
978-1-4051-4370-7 .
^ Maron BA, Leopold JA (September 2008).
"Mineralocorticoid receptor antagonists and endothelial function" . Current Opinion in Investigational Drugs . 9 (9): 963–969.
PMC
2967484 .
PMID
18729003 .
^ International Agency for Research on Cancer; World Health Organization (2001).
Some Thyrotropic Agents . World Health Organization. pp. 325–.
ISBN
978-92-832-1279-9 .
^ Agusti G, Bourgeois S, Cartiser N, Fessi H, Le Borgne M, Lomberget T (January 2013). "A safe and practical method for the preparation of 7α-thioether and thioester derivatives of spironolactone". Steroids . 78 (1): 102–107.
doi :
10.1016/j.steroids.2012.09.005 .
PMID
23063964 .
S2CID
8992318 .
^
a
b William Andrew Publishing (22 October 2013).
Pharmaceutical Manufacturing Encyclopedia, 3rd Edition . Elsevier. pp. 804–.
ISBN
978-0-8155-1856-3 .
^
"List of Aldosterone receptor antagonists" . Drugs.com .
^
"Potassium Uses, Side Effects & Interactions" . Drugs.com .
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