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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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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. |
format | Online Article Text |
id | pubmed-9826033 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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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