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A novel transdermal ketoprofen formulation for analgesia in cattle

Ketoprofen is registered in many countries for injectable administration in cattle. Because it is soluble in a wide range of excipients, development of a novel transdermal (TD) ketoprofen formulation was pursued to provide a convenient and pain‐free route of administration in cattle. One hundred and...

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Autores principales: Mills, Paul C., Owens, Jane G., Reinbold, James B., McGowan, Michael, Ellenbergner, Claudia, Woldeyohannes, Solomon, Satake, Nana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9826033/
https://www.ncbi.nlm.nih.gov/pubmed/36057922
http://dx.doi.org/10.1111/jvp.13093
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author Mills, Paul C.
Owens, Jane G.
Reinbold, James B.
McGowan, Michael
Ellenbergner, Claudia
Woldeyohannes, Solomon
Satake, Nana
author_facet Mills, Paul C.
Owens, Jane G.
Reinbold, James B.
McGowan, Michael
Ellenbergner, Claudia
Woldeyohannes, Solomon
Satake, Nana
author_sort Mills, Paul C.
collection PubMed
description Ketoprofen is registered in many countries for injectable administration in cattle. Because it is soluble in a wide range of excipients, development of a novel transdermal (TD) ketoprofen formulation was pursued to provide a convenient and pain‐free route of administration in cattle. One hundred and six excipient combinations were screened using in vitro techniques (Franz diffusion cells), with a 20%((w/v)) ketoprofen formulation dissolved in a combination of 45%:45%((v/v)) ethanol and isopropyl myristate (IPM) and 10%((v/v)) eucalyptus oil achieving maximal penetration of ketoprofen through bovine skin. A bioavailability study was then conducted using a randomized cross‐over design (n = 12), including IV, IM (both 3 mg/kg) and TD (10 mg/kg) ketoprofen formulations administered with a one‐week washout period between administrations. The IV and IM formulation pharmacokinetic results were as expected. The C (MAX), T (max and) AUC(0‐Last) were significantly higher (arithmetic mean ± SD) after TD administration (20.0 ± 6.5 μg/ml, 115 ± 17 min and 3940 ± 1324 μg*min/ml, respectively), compared to IM (11.0 ± 4.0 μg/ml, 74 ± 43 min and 2376 ± 738 μg*min/ml, respectively), although there were no significant differences for T(½β). However, dose corrected values C (MAX) and AUC(inf) were significantly higher for IM compared to TD. The arithmetic mean bioavailability (F) of the transdermal formulation was 50%. The plasma concentration of the TD formulation at a dose of 10 mg/kg was similar to the IM formulation at 3 mg/kg by 30 min post‐dosing with an arithmetic mean ± SD of 7.97 ± 4.38 vs. 8.02 ± 3.55 μg/ml, respectively. The TD formulation was generally well tolerated by cattle, although some local irritation along the site of application was noted after 12 h of exposure during the bioavailability study. Results indicate that this novel TD formulation provides a substantial improvement in administration convenience, may improve animal welfare and end‐user safety through needle‐free administration, and achieves similar plasma pharmacokinetics to the IM product when administered at 10 mg/kg.
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spelling pubmed-98260332023-01-09 A novel transdermal ketoprofen formulation for analgesia in cattle Mills, Paul C. Owens, Jane G. Reinbold, James B. McGowan, Michael Ellenbergner, Claudia Woldeyohannes, Solomon Satake, Nana J Vet Pharmacol Ther Original Articles Ketoprofen is registered in many countries for injectable administration in cattle. Because it is soluble in a wide range of excipients, development of a novel transdermal (TD) ketoprofen formulation was pursued to provide a convenient and pain‐free route of administration in cattle. One hundred and six excipient combinations were screened using in vitro techniques (Franz diffusion cells), with a 20%((w/v)) ketoprofen formulation dissolved in a combination of 45%:45%((v/v)) ethanol and isopropyl myristate (IPM) and 10%((v/v)) eucalyptus oil achieving maximal penetration of ketoprofen through bovine skin. A bioavailability study was then conducted using a randomized cross‐over design (n = 12), including IV, IM (both 3 mg/kg) and TD (10 mg/kg) ketoprofen formulations administered with a one‐week washout period between administrations. The IV and IM formulation pharmacokinetic results were as expected. The C (MAX), T (max and) AUC(0‐Last) were significantly higher (arithmetic mean ± SD) after TD administration (20.0 ± 6.5 μg/ml, 115 ± 17 min and 3940 ± 1324 μg*min/ml, respectively), compared to IM (11.0 ± 4.0 μg/ml, 74 ± 43 min and 2376 ± 738 μg*min/ml, respectively), although there were no significant differences for T(½β). However, dose corrected values C (MAX) and AUC(inf) were significantly higher for IM compared to TD. The arithmetic mean bioavailability (F) of the transdermal formulation was 50%. The plasma concentration of the TD formulation at a dose of 10 mg/kg was similar to the IM formulation at 3 mg/kg by 30 min post‐dosing with an arithmetic mean ± SD of 7.97 ± 4.38 vs. 8.02 ± 3.55 μg/ml, respectively. The TD formulation was generally well tolerated by cattle, although some local irritation along the site of application was noted after 12 h of exposure during the bioavailability study. Results indicate that this novel TD formulation provides a substantial improvement in administration convenience, may improve animal welfare and end‐user safety through needle‐free administration, and achieves similar plasma pharmacokinetics to the IM product when administered at 10 mg/kg. John Wiley and Sons Inc. 2022-09-04 2022-11 /pmc/articles/PMC9826033/ /pubmed/36057922 http://dx.doi.org/10.1111/jvp.13093 Text en © 2022 The Authors. Journal of Veterinary Pharmacology and Therapeutics published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Mills, Paul C.
Owens, Jane G.
Reinbold, James B.
McGowan, Michael
Ellenbergner, Claudia
Woldeyohannes, Solomon
Satake, Nana
A novel transdermal ketoprofen formulation for analgesia in cattle
title A novel transdermal ketoprofen formulation for analgesia in cattle
title_full A novel transdermal ketoprofen formulation for analgesia in cattle
title_fullStr A novel transdermal ketoprofen formulation for analgesia in cattle
title_full_unstemmed A novel transdermal ketoprofen formulation for analgesia in cattle
title_short A novel transdermal ketoprofen formulation for analgesia in cattle
title_sort novel transdermal ketoprofen formulation for analgesia in cattle
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9826033/
https://www.ncbi.nlm.nih.gov/pubmed/36057922
http://dx.doi.org/10.1111/jvp.13093
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