Metabolic effects of high dose amiloride and spironolactone: a comparative study in normal subjects

Amiloride (75 mg daily) and spironolactone (300 mg daily) were given to five normal subjects for 7 days in order to compare metabolic effects at maximal doses. Blood pressure, body weight, Na+ and K+ balance, and plasma concentrations of Na+, K+, active and total renin, angiotensin II, aldosterone, 11-deoxycorticosterone (DOC), 18-hydroxydeoxycorticosterone (18-OH DOC), corticosterone (B), 18-hydroxycorticosterone (18-OH B) and cortisol were measured before and on each day of treatment. Natriuresis and K+ retention were significantly greater with amiloride. Plasma K+ increased from 4.1 +/- 0.2 to 4.9 +/- 0.2 mmol/l (mean +/- s.d.) on amiloride and from 4.0 +/- 0.2 to 4.4 +/- 0.2 mmol/l with spironolactone. Stimulation of renin, angiotensin II, aldosterone and 18-OH B occurred with both drugs but was greater with amiloride in each case. A transient decrease in systolic and diastolic blood pressure was observed after 2 days of spironolactone treatment but not with amiloride. The slope of the regression of aldosterone on angiotensin II during spironolactone treatment was less than that with amiloride, consistent with partial blockade of aldosterone synthesis by spironolactone. These data suggest that the maximum metabolic effects of amiloride exceed those of spironolactone.