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Bioavailability of ...
Bioavailability of subcutaneous and intramuscular administrated buprenorphine in New Zealand White rabbits
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- Askar, Raad (author)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut,Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, Stockholm, Sweden
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- Fredriksson, Elin (author)
- Swedish Univ Agr Sci, Dept Clin Sci, POB 7054, SE-75007 Uppsala, Sweden
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- Manell, Elin (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för kliniska vetenskaper (KV),Department of Clinical Sciences
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- Hedeland, Mikael (author)
- Uppsala universitet,Analytisk farmaceutisk kemi,Natl Vet Inst, Dept Chem Environm & Feed Hyg, SVA, Uppsala, Sweden
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- Bondesson, Ulf (author)
- Uppsala universitet,Analytisk farmaceutisk kemi,Natl Vet Inst, Dept Chem Environm & Feed Hyg, SVA, Uppsala, Sweden
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- Bate, Simon (author)
- GlaxoSmithKline Med Res Ctr, CMC Stat, Stevenage, Herts, England
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- Olsén, Lena (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för kliniska vetenskaper (KV),Department of Clinical Sciences
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- Hedenqvist, Patricia (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för kliniska vetenskaper (KV),Department of Clinical Sciences
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(creator_code:org_t)
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- 2020-11-11
- 2020
- English.
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In: BMC Veterinary Research. - : Springer Science and Business Media LLC. - 1746-6148. ; 16:1
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Abstract
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- BackgroundBuprenorphine 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.ResultsThe area under the time concentration curve (AUC0-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).ConclusionsThe 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
- LANTBRUKSVETENSKAPER -- Veterinärmedicin (hsv//swe)
- AGRICULTURAL SCIENCES -- Veterinary Science (hsv//eng)
- LANTBRUKSVETENSKAPER -- Veterinärmedicin -- Klinisk vetenskap (hsv//swe)
- AGRICULTURAL SCIENCES -- Veterinary Science -- Clinical Science (hsv//eng)
Keyword
- NZW rabbit
- Buprenorphine bioavailability
- Administration routes
- Opioid pharmacokinetics
Publication and Content Type
- ref (subject category)
- art (subject category)
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