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Clinical pharmacology of torasemide, a new loop diuretic
Author(s) -
Brater D Craig,
Leinfelder Jeff,
Anderson Shirley A
Publication year - 1987
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.1987.131
Subject(s) - furosemide , probenecid , diuretic , pharmacology , pharmacokinetics , loop diuretic , nephron , pharmacodynamics , chemistry , drug interaction , urinary system , medicine , kidney , endocrinology
Torasemide is a new loop diuretic that potentially may have renal tubular effects from both the blood and urinary sides of the nephron. We assessed its pharmacokinetics and pharmacodynamics in eight normal subjects administering intravenous doses of 5, 10, and 20 mg compared with 40 mg furosemide. We assessed the effect of probenecid on response to the 20 mg dose. A dose intermediate to the 10 and 20 mg doses appeared equally natriuretic to 40 mg furosemide. Although total clearance was the same with all doses (about 0.45 ml/min/kg), renal clearance and the fraction of unchanged drug appearing in the urine decreased with higher doses raising the question of saturable renal secretion. Urinary dose‐response curves showed torasemide to be five times as potent as furosemide. Probenecid pretreatment decreased both urine volume (P = 0.0016) and sodium excretion (P = 0.0003), implying that delivery of drug to the urinary side of the nephron is the major determinant of response. Clinical Pharmacology and Therapeutics (1987) 42, 187–192; doi: 10.1038/clpt.1987.131