Evaluation of aldosterone antagonists in healthy man

The development of methods to allow the quantitative comparison of aldosterone antagonists in healthy men is reviewed. Pharmacological action is measured against a background of mineralocorticoid excess, induced either by administration of exogenous mineralocorticoid (usually aldosterone or fludrocortisone), or by stimulation of endogenous mineralocorticoid using salt restriction, diuretic administration, or a combination of the two. Use of fludrocortisone as the exogenous mineralocorticoid has proved convenient and useful, but the influence of aldosterone antagonists on potassium metabolism has proved somewhat inconstant in this experimental model. Repeated administration of a medium-potency diuretic appears to provide a clinically relevant situation in which the effect of aldosterone antagonists on potassium metabolism can be assessed. We describe these experimental methods in detail, discuss their applications, and make some suggestions for further research.