Pharmacokinetic and pharmacodynamic properties of orally administered torasemide in healthy cats

Abstract

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 Abbreviations: %D, fraction of the dose eliminated in urine; AUC INF , area under the concentration-time curve extrapolated to infinity; CHF, congestive heart failure; Cl, chloride; Cl R , renal clearance; Cmax, maximal plasma concentration; D, actual administered dose; E, excreted urine volume in 24 hours; Emax, maximum urine volume excreted in 24 hours; EX50, eliminated urinary amount of torasemide which induces an excreted urine volume of half of the Emax; F, absolute bioavailability; Fu, absolute bioavailability with urine data; HDO, high definition oscillometry; HF, heart failure; K, potassium; MRT INF , mean residence time extrapolated to infinity; Na, sodium; pCr, plasma creatinine; RAAS, renin-angiotensin-aldosterone system; T ½λz , mean terminal half-life;T max , Time to reach maximum plasma concentration; uAldo : C, urine aldosterone : creatinine ratio; uCr urinary, creatinin; USG, urine specific gravity; V ss mean, volume of distribution; X u total, eliminated urinary amount of torasemide in 24 hours; X ∞ u , total eliminated urinary amount of torasemide in 24 hours extrapolated to infinity.