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Bioavailability of subcutaneous and intramuscular administrated buprenorphine in New Zealand White rabbits

BACKGROUND: Buprenorphine is one of the most used analgesics for postoperative pain in rabbits. The recommended dose in rabbits (0.01–0.05 mg/kg) is the same for intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration, despite lack of pharmacokinetic data. Five male and five femal...

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Autores principales: Askar, Raad, Fredriksson, Elin, Manell, Elin, Hedeland, Mikael, Bondesson, Ulf, Bate, Simon, Olsén, Lena, Hedenqvist, Patricia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656698/
https://www.ncbi.nlm.nih.gov/pubmed/33176781
http://dx.doi.org/10.1186/s12917-020-02618-7
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author Askar, Raad
Fredriksson, Elin
Manell, Elin
Hedeland, Mikael
Bondesson, Ulf
Bate, Simon
Olsén, Lena
Hedenqvist, Patricia
author_facet Askar, Raad
Fredriksson, Elin
Manell, Elin
Hedeland, Mikael
Bondesson, Ulf
Bate, Simon
Olsén, Lena
Hedenqvist, Patricia
author_sort Askar, Raad
collection PubMed
description BACKGROUND: Buprenorphine is one of the most used analgesics for postoperative pain in rabbits. The recommended dose in rabbits (0.01–0.05 mg/kg) is the same for intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration, despite lack of pharmacokinetic data. Five male and five female New Zealand White rabbits (mean ± SD body weight 3.1 ± 0.3 kg) were administered 0.05 mg/kg buprenorphine by the IV, IM and SC routes and 0.1 mg/kg by the SC route, in a cross-over design with two-week wash-out periods between treatments. Blood was collected before, and up to 8 h post buprenorphine injection, for determination of serum levels by UPHLC-MS/MS. RESULTS: The area under the time concentration curve (AUC(0-t)) was lower after SC (398 ± 155 ng/mL/min) than IM (696 ± 168 ng/mL/min, p < 0.001) and IV (789 ± 189 ng/mL/min, p < 0.001) administration. The maximum serum concentration was lower after SC (2.2 ± 1.4 ng/mL) than after IM (11 ± 3.2 ng/mL) administration (p < 0.001). The bioavailability was lower after SC (50 ± 19%) than after IM (95 ± 21%) administration (p = 0.006). The elimination half-life was longer after SC (260 ± 120 min) than after IM (148 ± 26 min, p = 0.002) as well as IV (139 ± 33 min) injection (p < 0.001). An increase in the SC dose from 0.05 to 0.1 mg/kg resulted in an increase in the area under the time concentration curve of 50% in female (p = 0.022) and 165% in male rabbits (p < 0.001). The bioavailability did not change in the females (36 ± 14%, p = 0.6), whereas it increased in the males (71 ± 23%, p = 0.008). CONCLUSIONS: The lower bioavailability of 0.05 mg/kg buprenorphine after SC administration could explain the lack of efficacy seen in clinical pain studies in rabbits, using this route. For immediate pain relief, IV or IM administration is therefore be recommended, whereas SC administration may be useful to sustain analgesic serum levels, once efficient pain relief has been achieved. The current data do not support an increase in dose to compensate for the lower SC bioavailability. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12917-020-02618-7.
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spelling pubmed-76566982020-11-12 Bioavailability of subcutaneous and intramuscular administrated buprenorphine in New Zealand White rabbits Askar, Raad Fredriksson, Elin Manell, Elin Hedeland, Mikael Bondesson, Ulf Bate, Simon Olsén, Lena Hedenqvist, Patricia BMC Vet Res Research Article BACKGROUND: Buprenorphine is one of the most used analgesics for postoperative pain in rabbits. The recommended dose in rabbits (0.01–0.05 mg/kg) is the same for intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration, despite lack of pharmacokinetic data. Five male and five female New Zealand White rabbits (mean ± SD body weight 3.1 ± 0.3 kg) were administered 0.05 mg/kg buprenorphine by the IV, IM and SC routes and 0.1 mg/kg by the SC route, in a cross-over design with two-week wash-out periods between treatments. Blood was collected before, and up to 8 h post buprenorphine injection, for determination of serum levels by UPHLC-MS/MS. RESULTS: The area under the time concentration curve (AUC(0-t)) was lower after SC (398 ± 155 ng/mL/min) than IM (696 ± 168 ng/mL/min, p < 0.001) and IV (789 ± 189 ng/mL/min, p < 0.001) administration. The maximum serum concentration was lower after SC (2.2 ± 1.4 ng/mL) than after IM (11 ± 3.2 ng/mL) administration (p < 0.001). The bioavailability was lower after SC (50 ± 19%) than after IM (95 ± 21%) administration (p = 0.006). The elimination half-life was longer after SC (260 ± 120 min) than after IM (148 ± 26 min, p = 0.002) as well as IV (139 ± 33 min) injection (p < 0.001). An increase in the SC dose from 0.05 to 0.1 mg/kg resulted in an increase in the area under the time concentration curve of 50% in female (p = 0.022) and 165% in male rabbits (p < 0.001). The bioavailability did not change in the females (36 ± 14%, p = 0.6), whereas it increased in the males (71 ± 23%, p = 0.008). CONCLUSIONS: The lower bioavailability of 0.05 mg/kg buprenorphine after SC administration could explain the lack of efficacy seen in clinical pain studies in rabbits, using this route. For immediate pain relief, IV or IM administration is therefore be recommended, whereas SC administration may be useful to sustain analgesic serum levels, once efficient pain relief has been achieved. The current data do not support an increase in dose to compensate for the lower SC bioavailability. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12917-020-02618-7. BioMed Central 2020-11-11 /pmc/articles/PMC7656698/ /pubmed/33176781 http://dx.doi.org/10.1186/s12917-020-02618-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://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
Askar, Raad
Fredriksson, Elin
Manell, Elin
Hedeland, Mikael
Bondesson, Ulf
Bate, Simon
Olsén, Lena
Hedenqvist, Patricia
Bioavailability of subcutaneous and intramuscular administrated buprenorphine in New Zealand White rabbits
title Bioavailability of subcutaneous and intramuscular administrated buprenorphine in New Zealand White rabbits
title_full Bioavailability of subcutaneous and intramuscular administrated buprenorphine in New Zealand White rabbits
title_fullStr Bioavailability of subcutaneous and intramuscular administrated buprenorphine in New Zealand White rabbits
title_full_unstemmed Bioavailability of subcutaneous and intramuscular administrated buprenorphine in New Zealand White rabbits
title_short Bioavailability of subcutaneous and intramuscular administrated buprenorphine in New Zealand White rabbits
title_sort bioavailability of subcutaneous and intramuscular administrated buprenorphine in new zealand white rabbits
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656698/
https://www.ncbi.nlm.nih.gov/pubmed/33176781
http://dx.doi.org/10.1186/s12917-020-02618-7
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