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Plasma levels of a methadone constant rate infusion and their corresponding effects on thermal and mechanical nociceptive thresholds in dogs

BACKGROUND: The present study aimed to collect pharmacokinetic data of a methadone continuous rate infusion (CRI) and to investigate its effect on mechanical and thermal nociceptive thresholds. Seven, 47 to 54 months old beagle dogs, weighing 9.8 to 21.2 kg, were used in this experimental, randomize...

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Autores principales: Amon, T., Kästner, S. B. R., Kietzmann, M., Tünsmeyer, J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814539/
https://www.ncbi.nlm.nih.gov/pubmed/33461553
http://dx.doi.org/10.1186/s12917-020-02735-3
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author Amon, T.
Kästner, S. B. R.
Kietzmann, M.
Tünsmeyer, J.
author_facet Amon, T.
Kästner, S. B. R.
Kietzmann, M.
Tünsmeyer, J.
author_sort Amon, T.
collection PubMed
description BACKGROUND: The present study aimed to collect pharmacokinetic data of a methadone continuous rate infusion (CRI) and to investigate its effect on mechanical and thermal nociceptive thresholds. Seven, 47 to 54 months old beagle dogs, weighing 9.8 to 21.2 kg, were used in this experimental, randomized, blinded, placebo-controlled crossover study. Each dog was treated twice with either a methadone bolus of 0.2 mg kg(− 1) followed by a 0.1 mg kg(− 1) h(− 1) methadone CRI (group M) or an equivalent volume of isotonic saline solution (group P) for 72 h. Mechanical and thermal thresholds, as well as vital parameters and sedation were measured during CRI and for further 24 h. Blood samples for methadone plasma concentrations were collected during this 96 h period. RESULTS: Percentage thermal excursion (%TE) increased significantly from baseline (BL) until 3 h after discontinuation of CRI in M. Within P and between treatment groups differences were not significant. Mechanical threshold (MT) increased in M until 2 h after CRI discontinuation. Bradycardia and hypothermia occurred in M during drug administration and dogs were mildly sedated for the first 47 h. Decreased food intake and regurgitation were observed in M in five and four dogs, respectively. For methadone a volume of distribution of 10.26 l kg(− 1) and a terminal half-life of 2.4 h were detected and a clearance of 51.44 ml kg(− 1) min(− 1) was calculated. Effective methadone plasma concentrations for thermal and mechanical antinociception were above 17 ng ml(− 1). CONCLUSION: A methadone CRI of 0.1 mg kg(− 1) h(− 1) for 3 days after a loading dose results in steady anti-nociceptive effects in an acute pain model in healthy dogs. Main side effects were related to gastrointestinal tract, hypothermia, bradycardia and sedation.
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spelling pubmed-78145392021-01-19 Plasma levels of a methadone constant rate infusion and their corresponding effects on thermal and mechanical nociceptive thresholds in dogs Amon, T. Kästner, S. B. R. Kietzmann, M. Tünsmeyer, J. BMC Vet Res Research Article BACKGROUND: The present study aimed to collect pharmacokinetic data of a methadone continuous rate infusion (CRI) and to investigate its effect on mechanical and thermal nociceptive thresholds. Seven, 47 to 54 months old beagle dogs, weighing 9.8 to 21.2 kg, were used in this experimental, randomized, blinded, placebo-controlled crossover study. Each dog was treated twice with either a methadone bolus of 0.2 mg kg(− 1) followed by a 0.1 mg kg(− 1) h(− 1) methadone CRI (group M) or an equivalent volume of isotonic saline solution (group P) for 72 h. Mechanical and thermal thresholds, as well as vital parameters and sedation were measured during CRI and for further 24 h. Blood samples for methadone plasma concentrations were collected during this 96 h period. RESULTS: Percentage thermal excursion (%TE) increased significantly from baseline (BL) until 3 h after discontinuation of CRI in M. Within P and between treatment groups differences were not significant. Mechanical threshold (MT) increased in M until 2 h after CRI discontinuation. Bradycardia and hypothermia occurred in M during drug administration and dogs were mildly sedated for the first 47 h. Decreased food intake and regurgitation were observed in M in five and four dogs, respectively. For methadone a volume of distribution of 10.26 l kg(− 1) and a terminal half-life of 2.4 h were detected and a clearance of 51.44 ml kg(− 1) min(− 1) was calculated. Effective methadone plasma concentrations for thermal and mechanical antinociception were above 17 ng ml(− 1). CONCLUSION: A methadone CRI of 0.1 mg kg(− 1) h(− 1) for 3 days after a loading dose results in steady anti-nociceptive effects in an acute pain model in healthy dogs. Main side effects were related to gastrointestinal tract, hypothermia, bradycardia and sedation. BioMed Central 2021-01-18 /pmc/articles/PMC7814539/ /pubmed/33461553 http://dx.doi.org/10.1186/s12917-020-02735-3 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Amon, T.
Kästner, S. B. R.
Kietzmann, M.
Tünsmeyer, J.
Plasma levels of a methadone constant rate infusion and their corresponding effects on thermal and mechanical nociceptive thresholds in dogs
title Plasma levels of a methadone constant rate infusion and their corresponding effects on thermal and mechanical nociceptive thresholds in dogs
title_full Plasma levels of a methadone constant rate infusion and their corresponding effects on thermal and mechanical nociceptive thresholds in dogs
title_fullStr Plasma levels of a methadone constant rate infusion and their corresponding effects on thermal and mechanical nociceptive thresholds in dogs
title_full_unstemmed Plasma levels of a methadone constant rate infusion and their corresponding effects on thermal and mechanical nociceptive thresholds in dogs
title_short Plasma levels of a methadone constant rate infusion and their corresponding effects on thermal and mechanical nociceptive thresholds in dogs
title_sort plasma levels of a methadone constant rate infusion and their corresponding effects on thermal and mechanical nociceptive thresholds in dogs
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814539/
https://www.ncbi.nlm.nih.gov/pubmed/33461553
http://dx.doi.org/10.1186/s12917-020-02735-3
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