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Canrenone

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Canrenone
Skeletal formula of canrenone
Ball-and-stick model of the canrenone molecule
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
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.012.322 Edit this at Wikidata
Chemical and physical data
FormulaC22H28O3
Molar mass340.463 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 checkY
  • Key:UJVLDDZCTMKXJK-WNHSNXHDSA-N checkY
 ☒NcheckY (what is this?)  (verify)

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]

Pharmacology

Pharmacodynamics

Canrenone is reportedly more potent as an antimineralocorticoid relative to spironolactone, but is considerably less potent and effective as an antiandrogen.[11][12] 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.[13]

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 account for approximately 10 to 25% of the potassium-sparing effect of spironolactone,[14] whereas another metabolite, 7α-thiomethylspironolactone (7α-TMS), accounts for around 80% of the potassium-sparing effect of the drug.[15][16][17]

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.[18]

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][18]

Availability

Canrenone appears to remain available only in Italy, although potassium canrenoate remains marketed in various other countries as well.[19][20]

See also

References

  1. ^ Jürg Müller (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, Stubbs K, Smith M, Karim A (1989). "Spironolactone metabolism: steady-state serum levels of the sulfur-containing metabolites". J Clin Pharmacol. 29 (4): 342–7. doi:10.1002/j.1552-4604.1989.tb03339.x. PMID 2723123.
  3. ^ Losert, W; Casals-Stenzel, J; Buse, M (1985). "Progestogens with antimineralocorticoid activity". Arzneimittelforschung. 35 (2): 459–71. PMID 4039568.
  4. ^ Fernandez, MD; Carter, GD; Palmer, TN (1983). "The interaction of canrenone with oestrogen and progesterone receptors in human uterine cytosol". Br J Clin Pharmacol. 15 (1): 95–101. doi:10.1111/j.1365-2125.1983.tb01470.x. PMC 1427833. PMID 6849751.
  5. ^ a b c J. Elks (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.A.; Makin, H.L.J.; Kirk, D.N.; Murphy, G.M. (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): 772–3. 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, Michelle A.; Harvey, Richard A.; Finkel, Richard; Rey, Jose A.; Whalen, Karen (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 Endocrinol. 14 (2): 105–8. PMID 2761494.
  11. ^ Coelingh Benni, H.J.T.; Vemer, H.M. (15 December 1990). Chronic Hyperandrogenic Anovulation. CRC Press. pp. 152–. ISBN 978-1-85070-322-8.
  12. ^ Seldin, Donald W.; Giebisch, Gerhard H. (23 September 1997). Diuretic Agents: Clinical Physiology and Pharmacology. Academic Press. pp. 630–. ISBN 978-0-08-053046-8.
  13. ^ Colby, HD (1981). "Chemical suppression of steroidogenesis". Environ. Health Perspect. 38: 119–27. doi:10.1289/ehp.8138119. PMC 1568425. PMID 6786868.
  14. ^ Pere Ginés; Vicente Arroyo; Juan Rodés; Robert W. Schrier (15 April 2008). Ascites and Renal Dysfunction in Liver Disease: Pathogenesis, Diagnosis, and Treatment. John Wiley & Sons. p. 229. ISBN 978-1-4051-4370-7.
  15. ^ Maron BA, Leopold JA (2008). "Mineralocorticoid receptor antagonists and endothelial function". Curr Opin Investig Drugs. 9 (9): 963–9. PMC 2967484. PMID 18729003.
  16. ^ International Agency for Research on Cancer; World Health Organization (2001). Some Thyrotropic Agents. World Health Organization. pp. 325–. ISBN 978-92-832-1279-9.
  17. ^ Agusti G, Bourgeois S, Cartiser N, Fessi H, Le Borgne M, Lomberget T (2013). "A safe and practical method for the preparation of 7α-thioether and thioester derivatives of spironolactone". Steroids. 78 (1): 102–7. doi:10.1016/j.steroids.2012.09.005. PMID 23063964. S2CID 8992318.
  18. ^ a b William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia, 3rd Edition. Elsevier. pp. 804–. ISBN 978-0-8155-1856-3.
  19. ^ https://www.drugs.com/international/canrenone.html
  20. ^ https://www.drugs.com/international/potassium-canrenoate.html
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