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Canrenone

April 11, 2024

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 namesContaren, Luvion, Phanurane, Spiroletan
Other namesAldadiene;[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.comInternational Drug Names
Drug classAntimineralocorticoid
ATC code
Pharmacokinetic data
Protein binding95%
Elimination half-life16.5 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
  • 976-71-6 N
PubChem CID
  • 13789
ChemSpider
  • 13192 Y
UNII
  • 78O20X9J0U
ChEMBL
  • ChEMBL1463345 N
CompTox Dashboard (EPA)
  • DTXSID3045930
ECHA InfoCard100.012.322
Chemical and physical data
FormulaC22H28O3
Molar mass340.463 g·mol−1
3D model (JSmol)
  • Interactive image
  • 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
 NY (what is this?)  (verify)

Medical uses edit

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 edit

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 edit

Pharmacodynamics edit

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 edit

The elimination half-life of canrenone is about 16.5 hours.[2]

As a metabolite edit

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 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 edit

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 edit

Generic names edit

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

Brand names edit

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

Availability edit

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

See also edit

References edit

  1. ^ 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.
  2. ^ 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.
  3. ^ Losert W, Casals-Stenzel J, Buse M (1985). "Progestogens with antimineralocorticoid activity". Arzneimittel-Forschung. 35 (2): 459–471. PMID 4039568.
  4. ^ 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.
  5. ^ 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.
  6. ^ 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.
  7. ^ Romanelli RG, Gentilini P (May 2004). "Cross reactivity due to positive canrenone interference". Gut. 53 (5): 772–773. PMC 1774040. PMID 15082604.
  8. ^ a b c Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 167–. ISBN 978-3-88763-075-1.
  9. ^ 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.
  10. ^ 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.
  11. ^ 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.
  12. ^ 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.
  13. ^ Coelingh Benni H, Vemer H (15 December 1990). Chronic Hyperandrogenic Anovulation. CRC Press. pp. 152–. ISBN 978-1-85070-322-8.
  14. ^ Seldin DW, Giebisch GH (23 September 1997). Diuretic Agents: Clinical Physiology and Pharmacology. Academic Press. pp. 630–. ISBN 978-0-08-053046-8.
  15. ^ Colby HD (April 1981). "Chemical suppression of steroidogenesis". Environmental Health Perspectives. 38: 119–127. doi:10.1289/ehp.8138119. PMC 1568425. PMID 6786868.
  16. ^ 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.
  17. ^ 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.
  18. ^ International Agency for Research on Cancer; World Health Organization (2001). Some Thyrotropic Agents. World Health Organization. pp. 325–. ISBN 978-92-832-1279-9.
  19. ^ 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.
  20. ^ a b William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia, 3rd Edition. Elsevier. pp. 804–. ISBN 978-0-8155-1856-3.
  21. ^ "List of Aldosterone receptor antagonists". Drugs.com.
  22. ^ "Potassium Uses, Side Effects & Interactions". Drugs.com.

April 11, 2024
canrenone, sold, under, brand, names, contaren, luvion, phanurane, spiroletan, steroidal, antimineralocorticoid, spirolactone, group, related, spironolactone, which, used, diuretic, europe, including, italy, belgium, also, important, active, metabolite, spiron. 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 CanrenoneClinical dataTrade namesContaren Luvion Phanurane SpiroletanOther namesAldadiene 1 SC 9376 RP 11614 7a Desthioacetyl d6 spironolactone 6 7 Dehydro 7a desthioacetylspironolactone 17 Hydroxy 3 oxo 17a pregna 4 6 diene 21 carboxylic acid g lactoneAHFS Drugs comInternational Drug NamesDrug classAntimineralocorticoidATC codeC03DA03 WHO Pharmacokinetic dataProtein binding95 Elimination half life16 5 hours 2 IdentifiersIUPAC name 10 13 Dimethylspiro 2 8 9 11 12 14 15 16 octahydro 1H cyclopenta a phenanthrene 17 5 oxolane 2 3 dioneCAS Number976 71 6 NPubChem CID13789ChemSpider13192 YUNII78O20X9J0UChEMBLChEMBL1463345 NCompTox Dashboard EPA DTXSID3045930ECHA InfoCard100 012 322Chemical and physical dataFormulaC 22H 28O 3Molar mass340 463 g mol 13D model JSmol Interactive imageSMILES 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 CC5InChI 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 YKey UJVLDDZCTMKXJK WNHSNXHDSA N Y N Y what is this verify Contents 1 Medical uses 1 1 Heart failure 2 Pharmacology 2 1 Pharmacodynamics 2 2 Pharmacokinetics 2 3 As a metabolite 3 History 4 Society and culture 4 1 Generic names 4 2 Brand names 4 3 Availability 5 See also 6 ReferencesMedical uses editCanrenone 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 edit 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 editPharmacodynamics edit 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 11b hydroxylase cholesterol side chain cleavage enzyme 17a hydroxylase 17 20 lyase and 21 hydroxylase but once again is comparatively less potent in doing so 15 Pharmacokinetics edit The elimination half life of canrenone is about 16 5 hours 2 As a metabolite edit 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 7a thiomethylspironolactone 7a TMS accounts for around 80 of the potassium sparing effect of the drug 17 18 19 vte 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 lifeSpironolactone 72 ng mL 173 nmol L 80 ng mL 192 nmol L 231 ng hour mL 555 nmol hour L 1 4 hoursCanrenone 155 ng mL 455 nmol L 181 ng mL 532 nmol L 2 173 ng hour mL 6 382 nmol hour L 16 5 hours7a TMSTooltip 7a 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 hours6b OH 7a TMSTooltip 6b Hydroxy 7a 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 hoursSources See template History editCanrenone 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 editGeneric names edit Canrenone is the INNTooltip International Nonproprietary Name and USANTooltip United States Adopted Name of the drug 6 8 Brand names edit Canrenone has been marketed under the brand names Contaren Luvion Phanurane and Spiroletan among others 5 8 20 Availability edit Canrenone appears to remain available only in Italy although potassium canrenoate remains marketed in various other countries as well 21 22 See also editCanrenoic acid Potassium canrenoateReferences edit Muller J 6 December 2012 Regulation of Aldosterone Biosynthesis Physiological and Clinical Aspects Springer Science amp 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 amp 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 amp 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 Gines P Arroyo V Rodes J Schrier RW eds Ascites and Renal Dysfunction in Liver Disease Pathogenesis Diagnosis and Treatment John Wiley amp 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 7a 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 amp Interactions Drugs com Retrieved from https en wikipedia org w index php title Canrenone amp oldid 1190423566, wikipedia, wiki, book, books, library,

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