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Serum levetiracetam concentrations after transdermal levetiracetam administration, 3 times daily, to healthy cats

BACKGROUND: Repeated oral administration of antiepileptic drugs can be challenging for cat owners, resulting in reduced compliance, poor seizure control, and reduced quality of life for cats. Levetiracetam (LEV) has several properties that make it an appealing drug for transdermal application. OBJEC...

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Autores principales: Smith, Casey, Barnes Heller, Heidi L., Reif, Nicole, Van Hesteren, Matthew, Reinhart, Jennifer M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430925/
https://www.ncbi.nlm.nih.gov/pubmed/30663797
http://dx.doi.org/10.1111/jvim.15412
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author Smith, Casey
Barnes Heller, Heidi L.
Reif, Nicole
Van Hesteren, Matthew
Reinhart, Jennifer M.
author_facet Smith, Casey
Barnes Heller, Heidi L.
Reif, Nicole
Van Hesteren, Matthew
Reinhart, Jennifer M.
author_sort Smith, Casey
collection PubMed
description BACKGROUND: Repeated oral administration of antiepileptic drugs can be challenging for cat owners, resulting in reduced compliance, poor seizure control, and reduced quality of life for cats. Levetiracetam (LEV) has several properties that make it an appealing drug for transdermal application. OBJECTIVES: The aims were to (1) determine if transdermal LEV, in a lipophilic, liposomic cream vehicle, resulted in serum concentrations above 5 μg/mL; (2) identify clinical adverse effects; and (3) evaluate the concentration of LEV in a lipophilic liposomic cream at set intervals. ANIMALS: Six healthy, client‐owned cats weighing ≤5 kg. METHODS: Prospective clinical trial. Transdermal LEV was applied to the inner pinna at a dosage of 60 mg/kg (400 mg/mL concentration) at home for 6 days. Day 7, cats were hospitalized for blood sample collection for LEV concentration at times 0 (before dose administration), 0.5, 1, 2, 3, and 4 hours after administration. RESULTS: Median (range) timed serum concentrations were 16.6 (8.6‐39.6) μg/mL, 16.1 (6.8‐34.4) μg/mL, 15.4 (10.1‐36.7) μg/mL, 17.4 (9.2‐32.7) μg/mL, 15.1 (8.3‐25.9) μg/mL, and 14.8 (11.9‐28.4) μg/mL, respectively. Adverse events were limited to sedation (1/6 cats) and pinna crusting (1/6 cats). The LEV, in the proposed vehicle, retained concentration above 95% at 400 mg/mL up to 5 weeks. CONCLUSIONS AND CLINICAL IMPORTANCE: Thrice daily transdermal LEV resulted in median serum concentrations ≥5 μg/mL throughout the sampling period and clinical adverse events were minimal. Transdermal LEV can provide an alternative for cats resistant to administration of other forms of anticonvulsant medication.
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spelling pubmed-64309252019-04-04 Serum levetiracetam concentrations after transdermal levetiracetam administration, 3 times daily, to healthy cats Smith, Casey Barnes Heller, Heidi L. Reif, Nicole Van Hesteren, Matthew Reinhart, Jennifer M. J Vet Intern Med SMALL ANIMAL BACKGROUND: Repeated oral administration of antiepileptic drugs can be challenging for cat owners, resulting in reduced compliance, poor seizure control, and reduced quality of life for cats. Levetiracetam (LEV) has several properties that make it an appealing drug for transdermal application. OBJECTIVES: The aims were to (1) determine if transdermal LEV, in a lipophilic, liposomic cream vehicle, resulted in serum concentrations above 5 μg/mL; (2) identify clinical adverse effects; and (3) evaluate the concentration of LEV in a lipophilic liposomic cream at set intervals. ANIMALS: Six healthy, client‐owned cats weighing ≤5 kg. METHODS: Prospective clinical trial. Transdermal LEV was applied to the inner pinna at a dosage of 60 mg/kg (400 mg/mL concentration) at home for 6 days. Day 7, cats were hospitalized for blood sample collection for LEV concentration at times 0 (before dose administration), 0.5, 1, 2, 3, and 4 hours after administration. RESULTS: Median (range) timed serum concentrations were 16.6 (8.6‐39.6) μg/mL, 16.1 (6.8‐34.4) μg/mL, 15.4 (10.1‐36.7) μg/mL, 17.4 (9.2‐32.7) μg/mL, 15.1 (8.3‐25.9) μg/mL, and 14.8 (11.9‐28.4) μg/mL, respectively. Adverse events were limited to sedation (1/6 cats) and pinna crusting (1/6 cats). The LEV, in the proposed vehicle, retained concentration above 95% at 400 mg/mL up to 5 weeks. CONCLUSIONS AND CLINICAL IMPORTANCE: Thrice daily transdermal LEV resulted in median serum concentrations ≥5 μg/mL throughout the sampling period and clinical adverse events were minimal. Transdermal LEV can provide an alternative for cats resistant to administration of other forms of anticonvulsant medication. John Wiley and Sons Inc. 2019-01-21 2019 /pmc/articles/PMC6430925/ /pubmed/30663797 http://dx.doi.org/10.1111/jvim.15412 Text en © 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle SMALL ANIMAL
Smith, Casey
Barnes Heller, Heidi L.
Reif, Nicole
Van Hesteren, Matthew
Reinhart, Jennifer M.
Serum levetiracetam concentrations after transdermal levetiracetam administration, 3 times daily, to healthy cats
title Serum levetiracetam concentrations after transdermal levetiracetam administration, 3 times daily, to healthy cats
title_full Serum levetiracetam concentrations after transdermal levetiracetam administration, 3 times daily, to healthy cats
title_fullStr Serum levetiracetam concentrations after transdermal levetiracetam administration, 3 times daily, to healthy cats
title_full_unstemmed Serum levetiracetam concentrations after transdermal levetiracetam administration, 3 times daily, to healthy cats
title_short Serum levetiracetam concentrations after transdermal levetiracetam administration, 3 times daily, to healthy cats
title_sort serum levetiracetam concentrations after transdermal levetiracetam administration, 3 times daily, to healthy cats
topic SMALL ANIMAL
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430925/
https://www.ncbi.nlm.nih.gov/pubmed/30663797
http://dx.doi.org/10.1111/jvim.15412
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