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. 1976 Aug;3(4):607–612. doi: 10.1111/j.1365-2125.1976.tb04883.x

Canrenone-the principal active metabolite of spironolactone?

L E Ramsay, J R Shelton, D Wilkinson, M J Tidd
PMCID: PMC1428909  PMID: 22216502

Abstract

1 The properties of the aldosterone antagonists spironolactone and potassium canrenoate in tablet formulations were examined in two studies in healthy subjects, the first study comparing levels of their common major metabolite, canrenone, in plasma and the second study comparing the pharmacological activity of the two drugs in reversing the renal effects of the synthetic mineralocorticoid fludrocortisone.

2 At equal dosage by weight potassium canrenoate yielded peak levels and areas under the curve for canrenone in plasma which were significantly lower than those for spironolactone, and the peak level of canrenone was reached significantly later. Comparison with published work suggests that the experimental formulation of potassium canrenoate had low bioavailability.

3 Spironolactone produced statistically valid log dose-response curves against fludrocortisone as regards sodium excretion, potassium retention and increased urine sodium to potassium ratio. There was no significant log dose-reponse after potassium canrenoate, and a statistically valid estimate of relative potency could not be obtained.

4 The results of the two studies seem inconsistent with the view that canrenone alone is responsible for the pharmacological activity of both drugs, and suggest that a significant part of the activity of spironolactone may be attributable to metabolites other than canrenone.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BARGER A. C., BERLIN R. D., TULENKO J. F. Infusion of aldosterone, 9-alpha-fluorohydrocortisone and antidiuretic hormone into the renal artery of normal and adrenalectomized, unanesthetized dogs: effect on electrolyte and water excretion. Endocrinology. 1958 Jun;62(6):804–815. doi: 10.1210/endo-62-6-804. [DOI] [PubMed] [Google Scholar]
  2. DRILL V. A. The aldosterone blocking effects of spirolactones. Jpn J Pharmacol. 1962 Mar;11:77–87. doi: 10.1254/jjp.11.77. [DOI] [PubMed] [Google Scholar]
  3. Funder J. W., Feldman D., Highland E., Edelman I. S. Molecular modifications of anti-aldosterone compounds: effects on affinity of spirolactones for renal aldosterone receptors. Biochem Pharmacol. 1974 May 15;23(10):1493–1501. doi: 10.1016/0006-2952(74)90386-4. [DOI] [PubMed] [Google Scholar]
  4. GOCHMAN N., GANTT C. L. A fluorimetric method for the determination of a major spironolactone (Aldactone) metabolite in human plasma. J Pharmacol Exp Ther. 1962 Mar;135:312–316. [PubMed] [Google Scholar]
  5. GOLDFIEN A., LAIDLAW J. C., HAYDAR N. A., RENOLD A. E., THORN G. W. Fluorohydrocortisone and chlorohydrocortisone, highly potent derivatives of compound F. N Engl J Med. 1955 Mar 17;252(11):415–421. doi: 10.1056/NEJM195503172521101. [DOI] [PubMed] [Google Scholar]
  6. Herman T. S., Fimognari G. M., Edelman I. S. Studies on renal aldosterone-binding proteins. J Biol Chem. 1968 Jul 25;243(14):3849–3856. [PubMed] [Google Scholar]
  7. JOHNSON B. B. Bioassay of adrenal cortical steroids on the basis of electrolyte excretion by rats: effects of 11-desoxy and 11-oxy-steroids. Endocrinology. 1954 Feb;54(2):196–208. doi: 10.1210/endo-54-2-196. [DOI] [PubMed] [Google Scholar]
  8. KAGAWA C. M., BOUSKA D. J., ANDERSON M. L., KROL W. F. PHARMACOLOGICAL PROPERTIES OF A MINERALOCORTICOID ANTAGONIST (SC-14266). Arch Int Pharmacodyn Ther. 1964 May 1;149:8–24. [PubMed] [Google Scholar]
  9. KAGAWA C. M., BOUSKA D. J., ANDERSON M. L. RELATIONSHIP OF PLASMA ALDADIENE LEVELS AND ANTIMINERALOCORTICOID EFFECTS OF SPIRONOLACTONE IN THE LABORATORY. Proc Soc Exp Biol Med. 1964 Mar;115:837–840. doi: 10.3181/00379727-115-29052. [DOI] [PubMed] [Google Scholar]
  10. KAGAWA C. M. Blocking the renal electrolyte effects of mineralocorticoids with an orally active steroidal spirolactone. Endocrinology. 1960 Jul;67:125–132. doi: 10.1210/endo-67-1-125. [DOI] [PubMed] [Google Scholar]
  11. Karim A., Ranney R. E., Maibach H. I. Pharmacokinetic and metabolic fate of potassium canrenoate (SC-14266) in man. J Pharm Sci. 1971 May;60(5):708–715. doi: 10.1002/jps.2600600510. [DOI] [PubMed] [Google Scholar]
  12. Manitius A., Suchecki T. The mode of action and clinical use of spirolactones. Mater Med Pol. 1972 Apr-Jun;4(2):83–88. [PubMed] [Google Scholar]
  13. Mroczek W. J., Davidov M. E., Horoschak A., Finnerty F. A., Jr Canrenoate in normal man. Clin Pharmacol Ther. 1974 Aug;16(2):336–342. doi: 10.1002/cpt1974162336. [DOI] [PubMed] [Google Scholar]
  14. ROSS E. J. Human assay of electrolyte-active steroids and their antagonists. Clin Sci. 1962 Oct;23:197–202. [PubMed] [Google Scholar]
  15. Ramsay L. E., Hessian P., Tidd M. J. Bioassay of aldosterone antagonists in normal human subjects: a relationship between the level of plasma uric acid before treatment and apparent drug responses. Br J Clin Pharmacol. 1975 Jun;2(3):271–276. doi: 10.1111/j.1365-2125.1975.tb01587.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Sadée W., Dagcioglu M., Schröder R. Pharmacokinetics of spironolactone, canrenone and canrenoate-K in humans. J Pharmacol Exp Ther. 1973 Jun;185(3):686–695. [PubMed] [Google Scholar]
  17. Sadée W., Schröder R., von Leitner E., Dagcioglu M. Multiple dose kinetics of spironolactone and canrenoate-potassium in cardiac and hepatic failure. Eur J Clin Pharmacol. 1974;7(3):195–200. doi: 10.1007/BF00560381. [DOI] [PubMed] [Google Scholar]
  18. THORN G. W., SHEPPARD R. H., MORSE W. I., REDDY W. J., BEIGELMAN P. M., RENOLD A. E. Comparative action of aldosterone and 9-alpha-fluorohydrocortisone in man. Ann N Y Acad Sci. 1955 May 27;61(2):609–619. doi: 10.1111/j.1749-6632.1955.tb42514.x. [DOI] [PubMed] [Google Scholar]

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