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

Askar, Raad and Fredriksson, Elin and Hedeland, Mikael and Bondesson, Ulf and Bate, Simon and Olsén, Lena and Hedenqvist, Patricia (2020). Bioavailability of subcutaneous and intramuscular administrated buprenorphine in New Zealand White rabbits. BMC Veterinary Research. 16 , 436
[Research article]

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Abstract

Background Buprenorphine is one of the most used analgesics for postoperative pain in rabbits. The recommended dose in rabbits (0.01-0.05mg/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 (meanSD body weight 3.10.3kg) were administered 0.05mg/kg buprenorphine by the IV, IM and SC routes and 0.1mg/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 8h 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 +/- 155ng/mL/min) than IM (696 +/- 168ng/mL/min, p < 0.001) and IV (789 +/- 189ng/mL/min, p < 0.001) administration. The maximum serum concentration was lower after SC (2.2 +/- 1.4ng/mL) than after IM (11 +/- 3.2ng/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 +/- 120min) than after IM (148 +/- 26min, p=0.002) as well as IV (139 +/- 33min) injection (p < 0.001). An increase in the SC dose from 0.05 to 0.1mg/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 0.05mg/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.

Authors/Creators:Askar, Raad and Fredriksson, Elin and Hedeland, Mikael and Bondesson, Ulf and Bate, Simon and Olsén, Lena and Hedenqvist, Patricia
Title:Bioavailability of subcutaneous and intramuscular administrated buprenorphine in New Zealand White rabbits
Series Name/Journal:BMC Veterinary Research
Year of publishing :2020
Volume:16
Article number:436
Number of Pages:10
Publisher:BMC
ISSN:1746-6148
Language:English
Publication Type:Research article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 403 Veterinary Science > Clinical Science
Keywords:NZW rabbit, Buprenorphine bioavailability, Administration routes, Opioid pharmacokinetics
URN:NBN:urn:nbn:se:slu:epsilon-p-109750
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-109750
Additional ID:
Type of IDID
DOI10.1186/s12917-020-02618-7
Web of Science (WoS)000593860000001
ID Code:21238
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Clinical Sciences
Deposited By: SLUpub Connector
Deposited On:15 Jan 2021 09:43
Metadata Last Modified:14 Feb 2021 07:12

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