Pharmacokinetic and Metabolic Fate of Potassium Canrenoate (SC-14266) in Man

Karim, Aziz; Ranney, R. E.; Maibach, Howard I.

doi:10.1002/jps.2600600510

Cited by 43 publications

(14 citation statements)

References 9 publications

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“…After administration of this drug to man both canrenoate ( Figure 1) and canrenone are found in plasma (Karim, Ranney & Maibach, 1971). Evidence from in vitro studies (Funder, Feldman, Highland & Edelman, 1974) indicates that canrenoate has a low affinity for aldosteronebinding proteins, and is unlikely to contribute significantly to pharmacological activity.…”

Section: Introductionmentioning

confidence: 99%

Canrenone—the Principal Active Metabolite of Spironolactone?

Ramsay¹,

Shelton²,

Wilkinson³

et al. 1976

Brit J Clinical Pharma

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I 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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Section: Introductionmentioning

confidence: 99%

Canrenone—the Principal Active Metabolite of Spironolactone?

Ramsay¹,

Shelton²,

Wilkinson³

et al. 1976

Brit J Clinical Pharma

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“…administration of K-canrenoate, the resultant canrenoic acid has been found to be in enzymatic equilibrium with canrenone [6]. Canrenone can undergo hydrolysis back to canrenoic acid or be further metabolized and excreted in the urine [5]. To fully characterize all parameters in such a reversible system would require K-canrenoate and canrenone to be administered separately and concentrations of both compounds measured.…”

Section: Discussionmentioning

confidence: 99%

“…Because of its low aqueous solubility, spironolactone is only available for oral administration, whereas K-canrenoate, due to good solubility in aqueous media, is employed as an injectable agent with proposed doses of 1.43 Â spironolactone (taking account of higher potency of spironolactone on a milligram basis) [2][3][4][5][6]. K-canrenoate is instantaneously converted in the body to canrenoic acid, which is then rapidly converted to the biologically active metabolite canrenone.…”

Section: Introductionmentioning

confidence: 99%

Potassium canrenoate treatment in paediatric patients

Suyagh

Hawwa²,

Collier³

et al. 2013

Journal of Hypertension

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“…in the horse; in the guinea pig, rat, dog, and man the half-life was in the range of 26-3 1 hr. The disposition of intravenously administered radioactive potassium canrenoate in man was studied, and the elimination of the total radioactivity in the plasma was found to occur in three phases, with halflives of 0.073, 0.85, and 43.31 hr., respectively (1396). A pharmacokinetic model was presented to predict the detailed distribution and excretion of methotrexate in several mammalian species over a wide range of doses (1397).…”

Section: Biopharmaceuticsmentioning

confidence: 99%