Indacrinone: natriuretic and uricosuric effects of various ratios of its enantiomers in healthy men.

Indacrinone is an investigational loop-acting diuretic. To evaluate the natriuretic and uricosuric effects of varying ratios of its enantiomers, 10 healthy men, on a controlled Na+ (100 mEq) and K+ (80 mEq) diet, participated in a double-blind, randomized, balanced incomplete block, multiple-dose (one week) study of a fixed daily dose (10 mg) of (-) enantiomer combined with increasing doses (40, 90 and 140 mg) of (+) enantiomer versus 50 mg hydrochlorothiazide and placebo. On day 1, mean 24-h urinary Na+ increased (p less than 0.01) comparably (approximately 285 mEq) after each enantiomer combination and hydrochlorothiazide; however, the enantiomer combinations had marked uricosuric and hypouricemic effects that were enhanced with increased (+) enantiomer doses. By day 7, while enantiomer combinations and hydrochlorothiazide demonstrated comparable natriuretic activity, mean serum uric acid levels (mg/dl), in comparison to placebo, were increased (p less than 0.05) with hydrochlorothiazide but progressively decreased with increases in (+) enantiomer. Thus varying the ratio [(+, uricosuric): (-, natriuretic)] of the enantiomers of indacrinone caused natriuresis similar to hydrochlorothiazide, but had an opposite effect on serum uric acid.