Quantitative comparison of aldosterone antagonists in normal human subjects: prediction of therapeutic potency.
1 The potency of single doses of the aldosterone antagonist SC8109 relative to spironolactone in reversing the urinary electrolyte effects of fludrocortisone was examined in a double-blind, balanced, crossover study in six healthy volunteers. 2 For the urinary ratio log10 10Na/K, the relative potency of SC8109; spironolactone on a weight basis was 0.08:1 (95% confidence limits 0.04--0.13:1). 3 The potency of SC8109 relative to spironolactone for natriuresis and antikaliuresis was 0.10:1 and 0.05:1, respectively. 4 The results show excellent agreement with clinical experience where SC8109 was considered to have one tenth the potency of spironolactone. We suggest that the human bioassay employed in this study provides quantitative information which should be predictive of the therapeutic potency of aldosterone antagonists.
D000328:Adult; D001681:Biological Assay; D003404:Creatinine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology
D000451:Mineralocorticoid Receptor Antagonists; C032299:SC 8109; D013148:Spironolactone; D012964:Sodium; D003404:Creatinine; D011188:Potassium