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Dose‐independent pharmacokinetics of torasemide after intravenous and oral administration to rats
Author(s) -
Lee Dae Y.,
Kim Ji Y.,
Kim Yu C.,
Kwon Jong W.,
Kim Won B.,
Lee Myung G.
Publication year - 2005
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.447
Subject(s) - pharmacokinetics , oral administration , medicine , pharmacology
After intravenous (at doses of 1, 2, 5, and 10 mg/kg) and oral (at doses of 1, 5, and 10 mg/kg) administration of torasemide, the pharmacokinetic parameters were dose‐independent. Hence, the extent of absolute oral bioavailability ( F ) was also independent of oral doses; the values were 95.6, 98.8, and 97.3% for oral doses of 1, 5, and 10 mg/kg, respectively. The high F values indicated that the first‐pass (gastric, intestinal, and hepatic) effects of torasemide in rats could be almost negligible. After intravenous administration, the total body clearances of torasemide were extensively slower than the reported cardiac output in rats and hepatic extraction ratio was only 3–4% suggesting almost negligible first‐pass effects of torasemide in the heart, lung, and liver in rats. Based on in vitro rat tissue homogenate studies, the tissues studied also showed negligible metabolic activities for torasemide. Equilibrium of torasemide between plasma and blood cells of rat blood reached fast and plasma‐to‐blood cells concentration ratio was independent of initial blood concentrations of torasemide, 1, 5, and 10 µg/ml; the mean value was 0.279. Protein binding of torasemide to fresh rat plasma was 93.9±1.53% using an equilibrium dialysis technique. Copyright © 2005 John Wiley & Sons, Ltd.