Chemical compound
Pharmaceutical compound
Canrenone Clinical data Trade names Contaren, Luvion, Phanurane, Spiroletan Other names Aldadiene;[ 1] 6 -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 dataProtein binding 95% Eliminationhalf-life 16.5 hours[ 2] Identifiers 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 Chemical and physical data Formula C 22 H 28 O 3 Molar mass −1 3D model (JSmol ) 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
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Canrenone , sold under the brand namesContaren ,Luvion ,Phanurane , andSpiroletan , is asteroidal antimineralocorticoid [ 3] [ 4] spirolactone group related tospironolactone which is used as adiuretic inEurope , including inItaly andBelgium .[ 5] [ 6] [ 7] [ 8] active metabolite of spironolactone, and partially accounts for its therapeutic effects.[ 9] [ 2]
Canrenone has been found to be effective in the treatment ofhirsutism in women.[ 10]
Two studies of canrenone in people with heart failure have shown a mortality benefit compared to placebo. In the evaluation which studied people withchronic 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, andbrain 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]
Canrenone is reportedly more potent as an antimineralocorticoid relative to spironolactone, but is considerably less potent and effective as anantiandrogen .[ 13] [ 14] steroidogenic enzymes such as11β-hydroxylase ,cholesterol side-chain cleavage enzyme ,17α-hydroxylase ,17,20-lyase , and21-hydroxylase , but once again, is comparatively less potent in doing so.[ 15]
Theelimination half-life of canrenone is about 16.5 hours.[ 2]
Canrenone is anactive metabolite of spironolactone,canrenoic acid , andpotassium canrenoate , and is considered to be partially responsible for their effects.[ 9] potassium-sparing diuretic effect of spironolactone,[ 16] 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.
Canrenone was described and characterized in 1959.[ 5] potassium canrenoate (thepotassium salt ofcanrenoic acid ), by 1968.[ 20]
Society and culture [ edit ] Canrenone is theINN Tooltip International Nonproprietary Name andUSAN Tooltip United States Adopted Name of the drug.[ 6] [ 8]
Canrenone has been marketed under the brand names Contaren, Luvion, Phanurane, and Spiroletan, among others.[ 5] [ 8] [ 20]
Canrenone appears to remain available only inItaly , although potassium canrenoate remains marketed in various other countries as well.[ 21] [ 22]
^ Müller J (6 December 2012).Regulation of Aldosterone Biosynthesis: Physiological and Clinical Aspects 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 ISBN 978-1-4757-2085-3 ^a b Hill R, Makin H, Kirk D, Murphy G (23 May 1991).Dictionary of Steroids 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 ISBN 978-3-88763-075-1 ^a b Clark MA, Harvey RA, Finkel R, Rey JA, Whalen K (15 December 2011).Pharmacology 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 ISBN 978-1-85070-322-8 ^ Seldin DW, Giebisch GH (23 September 1997).Diuretic Agents: Clinical Physiology and Pharmacology ISBN 978-0-08-053046-8 ^ Colby HD (April 1981)."Chemical suppression of steroidogenesis" .Environmental Health Perspectives .38 :119– 127.Bibcode :1981EnvHP..38..119C .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 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 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 ISBN 978-0-8155-1856-3 ^ "List of Aldosterone receptor antagonists" .Drugs.com .^ "Potassium Uses, Side Effects & Interactions" .Drugs.com .
Topics Metabolites Related drugs
MR Tooltip Mineralocorticoid receptor
PR Tooltip Progesterone receptor
Agonists Testosterone derivatives: Progestins:6,6-Difluoronorethisterone 6,6-Difluoronorethisterone acetate 17α-Allyl-19-nortestosterone Allylestrenol Altrenogest Chloroethynylnorgestrel Cingestol Danazol Desogestrel Dienogest Ethinylandrostenediol Ethisterone Ethynerone Etonogestrel Etynodiol Etynodiol diacetate Gestodene Gestrinone Levonorgestrel Levonorgestrel esters (e.g.,levonorgestrel butanoate )Lynestrenol Lynestrenol phenylpropionate Metynodiol Metynodiol diacetate Norelgestromin Norethisterone (norethindrone) Norethisterone esters (e.g.,norethisterone acetate ,norethisterone enanthate )Noretynodrel Norgesterone Norgestimate Norgestrel Norgestrienone Norvinisterone Oxendolone Quingestanol Quingestanol acetate Tibolone Tigestol Tosagestin ; Anabolic–androgenic steroids:11β-Methyl-19-nortestosterone 11β-Methyl-19-nortestosterone dodecylcarbonate 19-Nor-5-androstenediol 19-Nor-5-androstenedione 19-Nordehydroepiandrosterone Bolandiol Bolandiol dipropionate Bolandione Dimethisterone Dienedione Dienolone Dimethandrolone Dimethandrolone buciclate Dimethandrolone dodecylcarbonate Dimethandrolone undecanoate Dimethyldienolone Dimethyltrienolone Ethyldienolone Ethylestrenol (ethylnandrol) Methyldienolone Metribolone (R-1881) Methoxydienone (methoxygonadiene) Mibolerone Nandrolone Nandrolone esters (e.g.,nandrolone decanoate ,nandrolone phenylpropionate )Norethandrolone Normethandrone (methylestrenolone, normethandrolone, normethisterone) RU-2309 Tetrahydrogestrinone Trenbolone (trienolone) Trenbolone esters (e.g.,trenbolone acetate ,trenbolone enanthate )Trendione Trestolone Trestolone acetate MixedSPRMs Tooltip Selective progesterone receptor modulators ) Antagonists
mPR Tooltip Membrane progesterone receptor PAQR Tooltip Progestin and adipoQ receptor )
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