Bioassay of a new aldosterone antagonist and evaluation of a simple method of quantitative comparison.
The renal antimineralocorticoid activity of single oral doses of a new aldosterone antagonist OH OPC(ME)-K was compared to that of spironolactone in two studies in healthy men. OH OPC(ME)-K reversed the urinary electrolyte response to fludrocortisone in the period up to 16 hr after treatment, but it was less potent than spironolactone on a weight basis. The best estimate of the relative potency of OH OPC(ME)-K: spironolactone (derived from a simple protocol using equal single doses of the two drugs) was 0.60:1 (95% confidence limits 0.24:1 to 1.42:1), in good agreement with the estimate from a more complex three-dose parallel-line bioassay (0.61:1, 95% confidence limits 0.48:1 to 0.79:1). The results of simple single-dose studies can be used, with certain assumptions, to provide a useful estimate of the relative potency of new aldosterone antagonists at an early stage of development.
D004311:Double-Blind Method; D004573:Electrolytes / Q000652:urine; D005438:Fludrocortisone / Q000037:antagonists & inhibitors; D006801:Humans; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists; D011283:Pregnenes / Q000009:adverse effects / Q000494:pharmacology*; D013148:Spironolactone / Q000009:adverse effects / Q000494:pharmacology
D004573:Electrolytes; D000451:Mineralocorticoid Receptor Antagonists; D011283:Pregnenes; D013148:Spironolactone; C031320:SC 27169; D005438:Fludrocortisone