Antagonism of aldosterone in normal subjects by Ro 12-2503 and spironolactone.
The potency and efficacy of a single dose of a new aldosterone antagonist, potassium 17 a-hydroxy-6 beta, 7 beta-methylene-3-oxo-D-homo-17a alpha-pregna-4,16-diene-21-carboxylate (Ro 12-2503), in reversing the renal effects of exogenous aldosterone were compared to those of spironolactone, and placebo. The study was performed according to double-blind and crossover procedure in six healthy male subjects. Both drugs, spironolactone and Ro 12-2503, did not completely antagonize the effects of aldosterone. The efficacy of Ro 12-2503 in terms of the urinary Na+/K+ ratio and the urinary Na+ concentration was less than that of spironolactone. Spironolactone produced a slightly greater natriuresis, but the difference was not significant. The method described, based on standard bioassay techniques permits a comparison of the two drugs, and may prove useful in the screening and evaluation of aldosterone antagonists.
D000328:Adult; D003404:Creatinine / Q000652:urine; D004231:Diuresis / Q000187:drug effects; D004311:Double-Blind Method; D004326:Drinking; D004573:Electrolytes / Q000378:metabolism; D004798:Enzymes / Q000097:blood; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists; D009994:Osmolar Concentration; D011245:Pregnadienes / Q000494:pharmacology*; D013148:Spironolactone / Q000494:pharmacology*
D004573:Electrolytes; D004798:Enzymes; D000451:Mineralocorticoid Receptor Antagonists; D011245:Pregnadienes; D013148:Spironolactone; C033926:Ro 12-2503; D003404:Creatinine