Skip to main content
NCBI home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1982 Feb;13(2):187–194. doi: 10.1111/j.1365-2125.1982.tb01354.x

Comparison of prorenoate potassium and spironolactone after repeated doses and steady state plasma levels of active metabolites.

G T McInnes, J R Shelton, I R Harrison, R M Perkins, R F Palmer
PMCID: PMC1401979  PMID: 7059416

Abstract

1 After repeated single daily doses, the aldosterone antagonists prorenoate potassium and spironolactone were compared with regard to renal antimineralocorticoid activity, plasma potassium concentration and steady state plasma levels of their active metabolites, prorenone and canrenone respectively, in a balanced crossover study of twelve healthy subjects. 2 Following challenge with the mineralocorticoid, fludrocortisone, best estimates of the potency of prorenoate potassium relative to spironolactone were 3.6 (95% confidence limits 1.6-10.4) for urinary sodium excretion and 3.4 (95% confidence limits 2.0-6.5) for urinary log10 10Na/K. Estimates with respect to urinary potassium excretion and plasma potassium concentration were imprecise, confirming the limitations of the fludrocortisone model in the evaluation of aldosterone antagonists at steady state. 3 Both compounds exhibited directly proportional relationships between daily dose and steady state plasma levels of active metabolites. The approximate mean terminal elimination half-life of prorenone at steady state was 32.6 h (range 18-80 h).

Full text

PDF
187

Selected References

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

  1. Claire M., Rafestin-Oblin M. E., Michaud A., Roth-Meyer C., Corvol P. Mechanism of action of a new antialdosterone compound, prorenone. Endocrinology. 1979 Apr;104(4):1194–1200. doi: 10.1210/endo-104-4-1194. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Funder J. W., Mercer J., Hood J. SC 23992: radioreceptor assays for therapeutic and side effects. Clin Sci Mol Med Suppl. 1976 Dec;3:333s–334s. doi: 10.1042/cs051333s. [DOI] [PubMed] [Google Scholar]
  4. GANTT C. L., DYNIEWICZ J. M. QUANTITATION OF MINERALOCORTICOID ACTIVITY AND ANTAGONISM IN NORMAL SUBJECTS. Metabolism. 1963 Nov;12:1007–1011. [PubMed] [Google Scholar]
  5. 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]
  6. Hofmann L. M., Chinn L. J., Pedrera H. A., Krupnick M. I., Suleymanov O. D. Potassium prorenoate: a new steroidal aldosterone antagonist. J Pharmacol Exp Ther. 1975 Aug;194(2):450–456. [PubMed] [Google Scholar]
  7. JICK H., MORRISON R. S., MOORE E. W., CHALMERS T. C. Metabolic studies on the effects of sprinolacton. Metabolism. 1963 May;12:381–387. [PubMed] [Google Scholar]
  8. 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]
  9. Karim A., Zagarella J., Hribar J., Dooley M. Spironolactone. I. Disposition and metabolism. Clin Pharmacol Ther. 1976 Feb;19(2):158–169. doi: 10.1002/cpt1976192158. [DOI] [PubMed] [Google Scholar]
  10. Karim A., Zagarella J., Hutsell T. C., Chao A., Baltes B. J. Spironolactone. II. Bioavailability. Clin Pharmacol Ther. 1976 Feb;19(2):170–176. doi: 10.1002/cpt1976192170. [DOI] [PubMed] [Google Scholar]
  11. Karim A., Zagarella J., Hutsell T. C., Dooley M. Spironolactone. III. Canrenone--maximum and minimum steady-state plasma levels. Clin Pharmacol Ther. 1976 Feb;19(2):177–182. doi: 10.1002/cpt1976192177. [DOI] [PubMed] [Google Scholar]
  12. Levine D., Ramsay L., Auty R., Branch R., Tidd M. Antagonism of endogenous mineralocorticoids in normal subjects by prorenoate potassium and spironolactone. Eur J Clin Pharmacol. 1976 Mar 22;09(5-6):381–386. doi: 10.1007/BF00606552. [DOI] [PubMed] [Google Scholar]
  13. McInnes G. T., Shelton J. R., Harrison I. R. Steady-state relative potency of aldosterone antagonists: spironolactone and prorenoate. Clin Pharmacol Ther. 1981 May;29(5):679–686. doi: 10.1038/clpt.1981.95. [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., Harrison I. R., Shelton J. R., Tidd M. J. Paradoxical potassium excretion in response to aldosterone antagonists. Eur J Clin Pharmacol. 1977 Jan 3;11(2):101–105. doi: 10.1007/BF00562899. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Ramsay L. E., Hettiarachchi J. Spironolactone in thiazide-induced hypokalaemia: variable response between patients. Br J Clin Pharmacol. 1981 Feb;11(2):153–158. doi: 10.1111/j.1365-2125.1981.tb01119.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ramsay L. E., Shelton J. R., Tidd M. J. The pharmacodynamics of single doses of prorenoate potasssium and spironolactone in fludrocortisone treated normal subjects. Br J Clin Pharmacol. 1976 Jun;3(3):475–482. doi: 10.1111/j.1365-2125.1976.tb00624.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ramsay L., Asbury M., Shelton J., Harrison I. Spironolactone and canrenoate-K: relative potency at steady state. Clin Pharmacol Ther. 1977 May;21(5):602–609. doi: 10.1002/cpt1977215602. [DOI] [PubMed] [Google Scholar]
  20. Ramsay L., Harrison I., Shelton J., Tidd M. Relative potency of prorenoate and spironolactone in normal man. Clin Pharmacol Ther. 1975 Oct;18(4):391–400. doi: 10.1002/cpt1975184391. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Solymoss B., Tóth S., Varga S., Krajny M. The influence of spironolactone on its own biotransformation. Steroids. 1970 Sep;16(3):263–275. doi: 10.1016/s0039-128x(70)80112-x. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES