Effect of intravenous infusion time on the pharmacokinetics and pharmacodynamics of the same total dose of torasemide in rabbits

Abstract

The pharmacokinetics and pharmacodynamics of torasemide were evaluated after intravenous administration of the same total dose of torasemide at a dose of 1mg/kg to rabbits with different infusion times, 1 min (treatment I), 30 min (treatment II) and 2 h (treatment III). The loss of water and electrolytes in urine induced by torasemide was immediately replaced with infusion of an equal volume of lactated Ringer's solution. All the pharmacokinetic parameters of torasemide, such as total area under the plasma concentration-time curve from time zero to time infinity (AUC), total body clearance (CL), apparent volume of distribution at steady state (Vss), terminal half-life and mean residence time (MRT), were independent of infusion times. However, the 8 h urine output (235, 534 and 808 ml) and 8 h urinary excretion of sodium (24.2, 80.1 and 89.2 mmol) and chloride (27.1, 89.2 and 94.0 mmol) were significantly greater in treatments II and III than those in treatment I, although the total 8 h urinary excretion of unchanged torasemide (1210, 1210 and 1310 microg) were not significantly different among the three treatments. This could be due to the higher diuretic efficiencies in treatments II and III.

Pharmacokinetic and pharmacodynamic properties of orally administered torsemide in healthy horses

“…Torsemide has less diuretic resistance and anti‐aldosterone effects in dogs . Although bioavailability could not be calculated in our study because of unavailability of a torsemide formulation for IV use, it was absorbed after PO administration in all horses, reaching plasma concentrations similar to those observed in previous studies in dogs, rabbits, rats and humans . Our results showed that after a single dose of 6 mg/kg, plasma torsemide concentration reached a median C max of 10.14 µg/mL and time to reach peak plasma concentration was approximately 3 hours.…”

“…8 Although bioavailability could not be calculated in our study because of unavailability of a torsemide formulation for IV use, it was absorbed after PO administration in all horses, reaching plasma concentrations similar to those observed in previous studies in dogs, rabbits, rats and humans. 2,11,13,27,28 Our results showed that after a single dose of 6 mg/kg, plasma torsemide concentration reached a median C max of 10.14 mg/mL and time to reach peak plasma concentration was approximately 3 hours. In humans, peak plasma concentrations are obtained approximately 1 hour after PO torsemide administration 2 and in dogs, peak plasma concentrations were observed at 1.5 hours after drug administration.…”

“…As previously reported in humans, furosemide has considerable variability with regard to its absorption, which makes it difficult to predict how much furosemide will be absorbed by a given patient. In contrast, the absorption of torsemide in humans, dogs, and rabbits is nearly complete . By comparison, a previous pharmacokinetic study reported bioavailability ranging from 26 to 65% after a single PO dose of furosemide when compared with a higher bioavailability of 96% after PO administration of torsemide .…”

“…In contrast, the absorption of torsemide in humans, dogs, and rabbits is nearly complete. 13,16,27 By comparison, a previous pharmacokinetic study reported bioavailability ranging from 26 to 65% after a single PO dose of furosemide when compared with a higher bioavailability of 96% after PO administration of torsemide. 2 A recent pharmacokinetic and pharmacodynamic study of PO administered furosemide at 1 mg/kg in healthy horses showed extremely low bioavailability (approximately 5%), absorption was erratic, and diuresis was not induced.…”

Generalized data of criteria of risk factors for the use of the drug torasemide from the materials of its preclinical studies

“…Восьмичасовой диурез у крыс с почечной недостаточностью был достоверно меньше по сравнению с контрольными животными (22,0 мл/кг против 178 мл/кг). Однако восьмичасовая экскреция натрия, калия и хлоридов не отличалась [11,12].…”