Bioassay of aldosterone antagonists in normal human subjects: a relationship between the level of plasma uric acid before treatment and apparent drug responses.

Abstract

The activity of single doses of SC-23992, a new aldosterone antagonist, and spironolactone in reversing the effects of fludrocortisone on urinary electrolyte composition in normal subjects was compared with that of placebo in a double-blind crossover study. 2 SC-23992 (50 mg) and spironolactone (125 mg) each significantly increased sodium excretion and the sodium : potassium (Na/K) ratio, and decreased potassium excretion, when compared with placebo. The response to the two active drugs did not differ significantly. 3 The urine Na/K ratio, and log10 Na/K, in response to spironolactone correlated negatively with the level of plasma uric acid measured 12 h before treatment. Similar trends were present after SC-23992 and placebo treatments. 4 It is suggested that the correlations between plasma uric acid and apparent drug response reflect a correlation between plasma uric acid and the aldosterone secretion rate in normal subjects. The sensitivity of this method of bioassay may be improved by suppressing endogenous aldosterone prior to medication.