Improved method for comparative evaluation of aldosterone antagonists in healthy man.
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 cnarenoate 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.
D000328:Adult; D000450:Aldosterone / Q000494:pharmacology; D002191:Canrenoic Acid / Q000097:blood / Q000494:pharmacology; D004341:Drug Evaluation / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D012964:Sodium / Q000652:urine; D013148:Spironolactone / Q000097:blood / Q000494:pharmacology; D013997:Time Factors
D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000450:Aldosterone; D002191:Canrenoic Acid; D012964:Sodium; D011188:Potassium