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Pharmacokinetic and pharmacodynamic properties of orally administered torasemide in healthy cats



Background:

In people and dogs, torasemide has higher bioavailability, longer half-life, and longer duration of action than equivalent doses of furosemide but data regarding pharmacological properties of torasemide in cats are limited.


Objective:

To assess pharmacokinetic and pharmacodynamic parameters of torasemide in healthy cats, and to investigate the effects of a single administration of torasemide on indicators of diuresis, plasma creatinine concentration, blood pressure, electrolyte concentrations and markers of the renin-angiotensin-aldosterone system (RAAS).


Animals:

Six clinically healthy adult European shorthair cats.


Methods:

Randomized 4-period crossover design with 3 groups and 4 treatments. Pharmacokinetic parameters were obtained using a noncompartmental analysis, and the clinically effective dose was assessed using a Hill model.


Results:

Mean absolute bioavailability was estimated at 88.1%. Mean total body clearance was 3.64 mL/h/kg and mean terminal half-life was 12.9 hours. Urine output significantly increased after torasemide administration (P < .001). The urine sodium : potassium ratio (uNa : uK) paralleled and was statistically correlated to urine output (P < .001). Administration of a single torasemide dose led to a significant dose-dependent increase in urine aldosterone : creatinine ratio (uAldo : C; P < .001) and a transient decrease in plasma potassium concentration (P < .001) but did not affect blood pressure or plasma creatinine concentration.


Conclusions and clinical importance:

A single torasemide dose leads to a significant increase in diuresis and renin-angiotensin-aldosterone system (RAAS) activation in healthy cats, with high absolute bioavailability, and without clinically relevant adverse effects. Pharmacokinetic parameters indicate that once daily dosing of 0.27 mg/kg may be appropriate in a clinical setting.


Keywords:

congestive heart failure; diuretic; feline; hypertrophic cardiomyopathy.



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