Antihypertensive and biochemical effects of indacrinone enantiomers

The enantiomers of indacrinone (I), an investigational loop diuretic, have different pharmacologic activity. The (-) enantiomer is natriuretic, and the (+) enantiomer is uricosuric. To determine the antihypertensive effects and an isouricemic ratio of indacrinone enantiomers, 37 patients with sitting diastolic blood pressure (BP) between 90 and 104 mm Hg, after a 4-week placebo washout, randomly received one of the ratios of I enantiomers, namely -2.5/+80 mg (A), -5/+80 mg (B), -10/+80 mg (C) or placebo (P), once daily for 12 weeks in a double-blind, parallel study. The mean reductions (baseline-end of treatment) in BP of 23/8, 20/10 and 25/10 mm Hg with treatments A, B and C respectively were greater (p less than 0.01) than that on P (0/3). Initially, serum uric acid decreased with treatments A and B but not with C. Mean changes in serum uric acid were -0.3, -0.4, 0.2 and 0.3 mg/dl respectively with treatments A, B, C and P. The ratio of -10/+80 mg produced least variation in serum uric acid. Reduction in serum K+ and Cl- appeared to be dose related to (-) enantiomer. No serious adverse effects were reported. A 1:9 ratio of I enantiomers intended for wide-scale use as a diuretic also showed good antihypertensive activity, a favorable uric acid profile and absence of hepatic toxicity in 14 patients.