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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 paramet...

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Autores principales: Roche‐Catholy, Marine, Paepe, Dominique, Devreese, Mathias, Broeckx, Bart J. G., Woehrlé, Frederique, Schneider, Marc, de Salazar Alcala, Andrea Garcia, Hellemans, Arnaut, Smets, Pascale
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9511087/
https://www.ncbi.nlm.nih.gov/pubmed/35906901
http://dx.doi.org/10.1111/jvim.16500
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author Roche‐Catholy, Marine
Paepe, Dominique
Devreese, Mathias
Broeckx, Bart J. G.
Woehrlé, Frederique
Schneider, Marc
de Salazar Alcala, Andrea Garcia
Hellemans, Arnaut
Smets, Pascale
author_facet Roche‐Catholy, Marine
Paepe, Dominique
Devreese, Mathias
Broeckx, Bart J. G.
Woehrlé, Frederique
Schneider, Marc
de Salazar Alcala, Andrea Garcia
Hellemans, Arnaut
Smets, Pascale
author_sort Roche‐Catholy, Marine
collection PubMed
description 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.
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spelling pubmed-95110872022-09-30 Pharmacokinetic and pharmacodynamic properties of orally administered torasemide in healthy cats Roche‐Catholy, Marine Paepe, Dominique Devreese, Mathias Broeckx, Bart J. G. Woehrlé, Frederique Schneider, Marc de Salazar Alcala, Andrea Garcia Hellemans, Arnaut Smets, Pascale J Vet Intern Med SMALL ANIMAL 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. John Wiley & Sons, Inc. 2022-07-30 2022 /pmc/articles/PMC9511087/ /pubmed/35906901 http://dx.doi.org/10.1111/jvim.16500 Text en © 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle SMALL ANIMAL
Roche‐Catholy, Marine
Paepe, Dominique
Devreese, Mathias
Broeckx, Bart J. G.
Woehrlé, Frederique
Schneider, Marc
de Salazar Alcala, Andrea Garcia
Hellemans, Arnaut
Smets, Pascale
Pharmacokinetic and pharmacodynamic properties of orally administered torasemide in healthy cats
title Pharmacokinetic and pharmacodynamic properties of orally administered torasemide in healthy cats
title_full Pharmacokinetic and pharmacodynamic properties of orally administered torasemide in healthy cats
title_fullStr Pharmacokinetic and pharmacodynamic properties of orally administered torasemide in healthy cats
title_full_unstemmed Pharmacokinetic and pharmacodynamic properties of orally administered torasemide in healthy cats
title_short Pharmacokinetic and pharmacodynamic properties of orally administered torasemide in healthy cats
title_sort pharmacokinetic and pharmacodynamic properties of orally administered torasemide in healthy cats
topic SMALL ANIMAL
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9511087/
https://www.ncbi.nlm.nih.gov/pubmed/35906901
http://dx.doi.org/10.1111/jvim.16500
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