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Antihypertensive and Biochemical Effects of Indacrinone Enantiomers
Author(s) -
Jain Adesh K.,
Michael Ronald,
Ryan Jerome R.,
McMahon F. Gilbert
Publication year - 1984
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/j.1875-9114.1984.tb03375.x
Subject(s) - diuretic , enantiomer , uricosuric , chemistry , placebo , uric acid , blood pressure , pharmacology , endocrinology , medicine , hyperuricemia , stereochemistry , alternative medicine , pathology
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 < 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.