PMID- 33176781
OWN - NLM
STAT- MEDLINE
DCOM- 20210507
LR  - 20210731
IS  - 1746-6148 (Electronic)
IS  - 1746-6148 (Linking)
VI  - 16
IP  - 1
DP  - 2020 Nov 11
TI  - Bioavailability of subcutaneous and intramuscular administrated buprenorphine in 
      New Zealand White rabbits.
PG  - 436
LID - 10.1186/s12917-020-02618-7 [doi]
LID - 436
AB  - 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.
FAU - Askar, Raad
AU  - Askar R
AD  - Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm 
      University, Stockholm, Sweden.
FAU - Fredriksson, Elin
AU  - Fredriksson E
AD  - Department of Clinical Sciences, Swedish University of Agricultural Sciences, PO 
      Box 7054, SE-750 07, Uppsala, Sweden.
FAU - Manell, Elin
AU  - Manell E
AD  - Department of Clinical Sciences, Swedish University of Agricultural Sciences, PO 
      Box 7054, SE-750 07, Uppsala, Sweden.
FAU - Hedeland, Mikael
AU  - Hedeland M
AD  - Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden.
AD  - Department of Chemistry, Environment and Feed Hygiene, SVA, National Veterinary 
      Institute, Uppsala, Sweden.
FAU - Bondesson, Ulf
AU  - Bondesson U
AD  - Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden.
AD  - Department of Chemistry, Environment and Feed Hygiene, SVA, National Veterinary 
      Institute, Uppsala, Sweden.
FAU - Bate, Simon
AU  - Bate S
AD  - CMC Statistics, GlaxoSmithKline Medicines Research Centre, Stevenage, UK.
FAU - Olsen, Lena
AU  - Olsen L
AD  - Department of Clinical Sciences, Swedish University of Agricultural Sciences, PO 
      Box 7054, SE-750 07, Uppsala, Sweden.
FAU - Hedenqvist, Patricia
AU  - Hedenqvist P
AUID- ORCID: 0000-0003-4540-6250
AD  - Department of Clinical Sciences, Swedish University of Agricultural Sciences, PO 
      Box 7054, SE-750 07, Uppsala, Sweden. patricia.hedenqvist@slu.se.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20201111
PL  - England
TA  - BMC Vet Res
JT  - BMC veterinary research
JID - 101249759
RN  - 0 (Analgesics, Opioid)
RN  - 40D3SCR4GZ (Buprenorphine)
SB  - IM
EIN - BMC Vet Res. 2021 Apr 16;17(1):169. PMID: 33863335
MH  - Administration, Intravenous/veterinary
MH  - Analgesics, Opioid/*administration & dosage/blood/*pharmacokinetics
MH  - Animals
MH  - Biological Availability
MH  - Buprenorphine/*administration & dosage/blood/*pharmacokinetics
MH  - Cross-Over Studies
MH  - Female
MH  - Injections, Intramuscular/veterinary
MH  - Injections, Subcutaneous/veterinary
MH  - Male
MH  - Rabbits
PMC - PMC7656698
OTO - NOTNLM
OT  - Administration routes
OT  - Buprenorphine bioavailability
OT  - NZW rabbit
OT  - Opioid pharmacokinetics
COIS- The authors declare that they have no competing interests.
EDAT- 2020/11/13 06:00
MHDA- 2021/05/08 06:00
PMCR- 2020/11/11
CRDT- 2020/11/12 05:30
PHST- 2020/05/13 00:00 [received]
PHST- 2020/10/09 00:00 [accepted]
PHST- 2020/11/12 05:30 [entrez]
PHST- 2020/11/13 06:00 [pubmed]
PHST- 2021/05/08 06:00 [medline]
PHST- 2020/11/11 00:00 [pmc-release]
AID - 10.1186/s12917-020-02618-7 [pii]
AID - 2618 [pii]
AID - 10.1186/s12917-020-02618-7 [doi]
PST - epublish
SO  - BMC Vet Res. 2020 Nov 11;16(1):436. doi: 10.1186/s12917-020-02618-7.