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. 1975 The British Pharmacological Society