ATCvet code: QC03CA04.
Pharmacotherapeutic group: Pharmacotherapeutic group: Cardiovascular system, high-ceiling diuretics, plain sulfonamides.
Pharmacodynamics
Torasemide is a loop diuretic of the pyridyl sulfonylurea class. Torasemide is secreted into the tubule lumen via the probenecid-sensitive organic acid transport system. The main site of action is the medullary portion of the ascending limb of the loop of Henle. Loop diuretics mainly inhibit the Na+/2Cl-/K+ carrier from the luminal side of the cell.
Inhibition of sodium and chloride ion reabsorption not only results in saluresis but also in a decrease in interstitial osmolarity within the renal medulla. This in turn decreases free water reabsorption resulting in increased water excretion/urine production.
In healthy dogs and after once daily administration for 5 days, the mean percentage of increase in excreted urine over 24 hours ranged between 33% and 50% at 0.15 mg/kg, between 181% and 328% at 0.4 mg/kg and between 264% and 418% at 0.75 mg/kg.
Based on a pharmacodynamics modelling study conducted in healthy dogs at doses of 0.1 and 0.6 mg torasemide/kg, a single dose of torasemide had approximately 20 times the diuretic effect of a single dose of furosemide. Refer to Special precautions for use.
Pharmacokinetics
In dogs, after a single intravenous dose of 0.1 mg/kg, the total body clearance was 0.017 L/h·kg, the volume of distribution was 0.14 L/kg and the terminal half-life was 7.0 hours. After a single oral dose of 0.1 mg/kg, the oral absolute bioavailability corresponded to about 90%. The oral absorption was fast with mean Tmax at 0.93 hours after administration of 0.1 mg/kg. The maximum plasma concentrations Cmax corresponded to 1.1 mcg/mL after a single oral dose of 0.1 mg/kg and to 19 mcg/mL after a single oral dose of 1.6 mg/kg. The AUCinf corresponded to 6.3 mcg·h/mL after a single oral dose of 0.1mg/kg and to 153.6 mcg·h/mL after a single oral dose of 1.6 mg/kg. The plasma protein binding was > 98%. A large proportion of the dose (between 61% and 70%) is excreted in the urine as unchanged parent drug. Two metabolites (a dealkylated and a hydroxylated metabolite) were also identified in urine. The parent drug is metabolised by the hepatic cytochrome P450 family isoforms 3A4 and 2E1, and to a lesser extent by 2C9. Dose proportionality for Cmax and AUCinf was demonstrated between 0.2 and 1.6 mg/kg.
Feeding significantly increased torasemide AUClast by 36% on average and slightly delayed Tmax but no significant impact on Cmax was detected. After repeated administration to dogs at 0.2 mg/kg daily for 14 days, no plasma accumulation of torasemide was detected.