Indacrinone: modification of diuretic, uricosuric, and kaliuretic actions by amiloride

The response to indacrinone, a new indanone diuretic, was studied in 12 healthy subjects. Ten milligrams alone and in combination with either 2.5 mg or 5 mg amiloride was given in a randomized double-blind study with placebo control to study its action and to assess the optimum combination. Indacrinone alone induced an increase in urine flow rate and in sodium, potassium, and hydrogen ion excretion for at least 8 hr. Indacrinone also induced an initial uricosuria in the first 4 hr, followed by urate retention in the subsequent 12 to 24 hr, with no resultant change in the mean 24-hr urate excretion and minimal changes in the serum urate concentrations. The addition of 2.5 mg amiloride to the 10 mg indacrinone lowered potassium excretion to control levels, whereas addition of 5 mg amiloride resulted in net retention of potassium. With both doses of amiloride, the increased free hydrogen ion excretion after indacrinone returned to placebo levels. There were minor increases in serum creatinine, consistent with volume depletion due to the diuresis. There was a reduction in urinary calcium excretion. Our study shows that the combination of 10 mg indacrinone and 2.5 mg amiloride induces useful diuresis with minimal overall effect on urate, potassium, and hydrogen ion excretion.