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Pharmacology of enantiomers and (–) p‐OH metabolite of indacrinone
Author(s) -
Vlasses Peter H,
Irvin John D,
Huber Paul B,
Lee Robyn B,
Ferguson Roger K,
Schrogie John J,
Zacchei Anthony G,
Davies Richard O,
Abrams William B
Publication year - 1981
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1981.114
Subject(s) - probenecid , metabolite , diuretic , furosemide , pharmacology , natriuresis , chemistry , uric acid , enantiomer , placebo , sodium , medicine , biochemistry , stereochemistry , organic chemistry , alternative medicine , pathology
Indacrinone, a racemic mixture, is a loop‐blocking diuretic with effects on uric acid elimination that differ from those of furosemide. A series of studies in healthy men was undertaken to characterize the pharmacologic activity of the positive (+) and negative (–) enantiomers (E) of indacrinone and its (–) p‐OH metabolite, (–) MET. All subjects were on sodium‐ and potassium‐controlled diet; each experiment was similar in design and included placebo and positive controls. Oral (–)E and (–)MET exerted dose‐related natriuretic and diuretic effects; intravenous doses of (–)E were more effective than (–)MET. The effects of (–)E and (–)MET on serum uric acid were the same as those reported with indacrinone. After (–)E, both (–)E and generated (–)MET appeared to contribute to the natriuresis. (+)E induced dose‐related decreases in serum uric acid up to 24 hr after dosage; at the higher doses of (+)E, the hypouricemic effects were of the order of those after 500 mg of probenecid. Thus, indacrinone is a novel loop diuretic with enantiomers and a (–)MET, each of which has a different pharmacologic profile. Clinical Pharmacology and Therapeutics (1981) 29 , 798–807; doi: 10.1038/clpt.1981.114