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  • 1
    ISSN: 1432-1041
    Keywords: Aldosterone antagonists ; aldosterone infusion ; evaluation in man ; spironolactone ; potassium canrenoate ; spironolactone metabolites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A method of assessing the qualitative and quantitative activity of competitive aldosterone antagonists in healthy man is described. It requires intravenous infusion of aldosterone (0.5 mg/6 h), iv and oral water loading for six hours and fractionated collection of urine over eight hours. Aldosterone antagonists were administered orally 1.5 h before the start of the infusion (spironolactone 50, 200 or 800 mg) or added to the infused solution (potassium canrenoate 300, 600 or 1000–1200 mg). The effect was assessed by changes in urinary sodium and potassium excretion and in urinary Na+/K+ ratio. The plasma levels and urinary excretion of canrenone, canrenoate and canrenoate ester glucuronide, respectively, were determined after administration of spironolactone and potassium canrenoate. Between 4–8 h (spironolactone) or 2–8 h (potassium canrenoate) after commencement of the infusion there was linear, dose-dependent reversal of the mineralocorticoid-induced sodium retention and/or decrease in the Na+/K+ ratio. The plasma levels and urinary excretion of the metabolites measured were also dose-dependent. The method appears suitable for comparison of the potency of aldosterone antagonists and for defining the time course of drug action within the observation period employed.
    Type of Medium: Electronic Resource
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