Comparison of plasma levels and analgesic effect between oral transmucosal and subcutaneous administration of buprenorphine in rabbits
Rabbits are becoming more popular as pet animals and surgical procedures are likewise getting more common. Hence the need for postoperative analgesic treatment in the home is increasing. Buprenorphine is a partial µ-opioid receptor agonist with long duration and is the therefore useful as a postoper...
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| Formato: | H3 |
| Lenguaje: | Inglés sueco |
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SLU/Dept. of Clinical Sciences (until 231231)
2016
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| Materias: |
| _version_ | 1855571534818574336 |
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| author | Freijs, Emma |
| author_browse | Freijs, Emma |
| author_facet | Freijs, Emma |
| author_sort | Freijs, Emma |
| collection | Epsilon Archive for Student Projects |
| description | Rabbits are becoming more popular as pet animals and surgical procedures are likewise getting more common. Hence the need for postoperative analgesic treatment in the home is increasing. Buprenorphine is a partial µ-opioid receptor agonist with long duration and is the therefore useful as a postoperative analgesic agent. It is also the most commonly used opioid in rabbits. Buprenorphine has poor bioavailability after oral dosing, therefore oral transmucosal (OTM) administration could be an option for pet owners. The aim of this study was to compare OTM with subcutaneous (SC) administration of buprenorphine by buprenorphine plasma concentrations and facial pain expression scoring.
Eighteen female New Zealand White rabbits with the mean (SD) body weight 3.90 (0.49) kg were used in a study on bone replacement, in which a full diaphysis bone segment of 20 mm was removed from the radius and replaced by either a monetite implant or autologous bone. Buprenorphine was administered postoperatively either SC (0.05 mg/kg) or OTM (0.15 mg/kg) every eighth hour. Blood samples were collected before and at 8 time points (15-540 min) after the first administration of buprenorphine. Plasma was analysed for concentrations of buprenorphine with ultra-high performance liquid chromatography – tandem mass spectrometry. Photographs were taken of the rabbits’ faces prior to surgery and postoperatively before each blood sampling. The pictures were scored in a blinded fashion for pain assessment both subjectively and with the Rabbit Grimace Scale (RbtGs).
The OTM administration required large volumes and was difficult to accomplish. Buprenorphine plasma concentrations varied largely, especially after SC administration. The maximal plasma concentration (Cmax) and the area under the plasma concentration time curve (AUC) were significantly lower after OTM than after SC administration (p < 0.05). The median Cmax values were 0.74 ng/ml and 1.16 ng/ml, and the median AUC values were 41 ng·h/ml and 337 ng·h/ml, for OTM and SC administration respectively. Subjective pain and RbtGs scores were well correlated (OTM: ρ = 0.94 and SC: ρ = 0.90) but did not correlate with buprenorphine plasma concentrations. RbtGs pain scores for OTM administration were only significant higher (p < 0.05) at one time point (15 min) out of eight compared to SC administration.
In summary, neither of the administration routes were regarded as reliable as reflected by the large variation in plasma concentrations of buprenorphine. Buprenorphine given OTM was not as well absorbed as when administered SC given the plasma concentrations. More studies are needed to confirm these findings and to find other analgesic treatment alternatives that are owner-friendly. |
| format | H3 |
| id | RepoSLU9518 |
| institution | Swedish University of Agricultural Sciences |
| language | Inglés swe |
| publishDate | 2016 |
| publishDateSort | 2016 |
| publisher | SLU/Dept. of Clinical Sciences (until 231231) |
| publisherStr | SLU/Dept. of Clinical Sciences (until 231231) |
| record_format | eprints |
| spelling | RepoSLU95182016-09-22T12:51:23Z Comparison of plasma levels and analgesic effect between oral transmucosal and subcutaneous administration of buprenorphine in rabbits Jämförelse av plasmakoncentrationer och analgetisk effekt mellan oral transmukosal och subkutan administrering av buprenorfin hos kanin Freijs, Emma rabbit buprenorphine oral transmucosal subcutaneous drug administration analgesia pain scoring Rabbits are becoming more popular as pet animals and surgical procedures are likewise getting more common. Hence the need for postoperative analgesic treatment in the home is increasing. Buprenorphine is a partial µ-opioid receptor agonist with long duration and is the therefore useful as a postoperative analgesic agent. It is also the most commonly used opioid in rabbits. Buprenorphine has poor bioavailability after oral dosing, therefore oral transmucosal (OTM) administration could be an option for pet owners. The aim of this study was to compare OTM with subcutaneous (SC) administration of buprenorphine by buprenorphine plasma concentrations and facial pain expression scoring. Eighteen female New Zealand White rabbits with the mean (SD) body weight 3.90 (0.49) kg were used in a study on bone replacement, in which a full diaphysis bone segment of 20 mm was removed from the radius and replaced by either a monetite implant or autologous bone. Buprenorphine was administered postoperatively either SC (0.05 mg/kg) or OTM (0.15 mg/kg) every eighth hour. Blood samples were collected before and at 8 time points (15-540 min) after the first administration of buprenorphine. Plasma was analysed for concentrations of buprenorphine with ultra-high performance liquid chromatography – tandem mass spectrometry. Photographs were taken of the rabbits’ faces prior to surgery and postoperatively before each blood sampling. The pictures were scored in a blinded fashion for pain assessment both subjectively and with the Rabbit Grimace Scale (RbtGs). The OTM administration required large volumes and was difficult to accomplish. Buprenorphine plasma concentrations varied largely, especially after SC administration. The maximal plasma concentration (Cmax) and the area under the plasma concentration time curve (AUC) were significantly lower after OTM than after SC administration (p < 0.05). The median Cmax values were 0.74 ng/ml and 1.16 ng/ml, and the median AUC values were 41 ng·h/ml and 337 ng·h/ml, for OTM and SC administration respectively. Subjective pain and RbtGs scores were well correlated (OTM: ρ = 0.94 and SC: ρ = 0.90) but did not correlate with buprenorphine plasma concentrations. RbtGs pain scores for OTM administration were only significant higher (p < 0.05) at one time point (15 min) out of eight compared to SC administration. In summary, neither of the administration routes were regarded as reliable as reflected by the large variation in plasma concentrations of buprenorphine. Buprenorphine given OTM was not as well absorbed as when administered SC given the plasma concentrations. More studies are needed to confirm these findings and to find other analgesic treatment alternatives that are owner-friendly. Kaniner har blivit populära som husdjur och därmed har även operativa ingrepp ökat. I och med detta ökar behovet av smärtlindring på kanin i hemmet. Buprenorfin är en partiell agonist till µ-opioidreceptorn med lång duration och är därför användbar för postoperativ smärtlindring. Dessutom är det den vanligaste opioiden som ges till kanin. Buprenorfin har dålig oral biotillgänglighet därför skulle oral transmukosal administrering kunna vara ett alternativ för behandling i hemmet utfört av djurägare. Syftet med denna studie var att jämföra två olika administrationsvägar av buprenorfin, subkutan och oral transmukosal, genom att mäta plasmahalter av buprenorfin samt utvärdera smärta genom att bedöma ansiktsuttryck. Arton New Zealand White honkaniner med en medelkroppsvikt (SD) på 3,9 (0,49) kg användes i en experimentell studie av nybildning av benvävnad varvid 20 mm av radiusdiafysen avlägsnades och ersattes av ett monetitimplantat eller autologt ben. Buprenorfin administrerades postoperativt antingen subkutant (0,05 mg/kg) eller oralt transmukosalt (0,15 mg/kg) var åttonde timme. Blodprover togs före operation och vid 8 tidpunkter (15-540 min) efter den första buprenorfinadministrationen. Plasmahalter av buprenorfin analyserades med ultrahög-prestanda vätskekromatografi - tandem masspektrometri. Djurens ansikten fotograferades före operation samt före varje blodprovtagningstillfälle. Fotografierna bedömdes blindat för smärta både subjektivt och enligt en skala baserad på ansiktsuttryck hos kanin, Rabbit Grimace Scale (RbtGs). Oral transmukosal administrering krävde en stor volym och var svår att utföra. Plasmakoncentrationerna av buprenorfin varierade kraftigt, särskilt efter subkutan injektion. Den maximala plasmakoncentrationen (Cmax) och arean under plasmakoncentrationskurvan (AUC) var signifikant lägre efter oral transmukosal jämfört med subkutan administration (p <0,05). Medianvärden för Cmax var 0,74 ng/ml för oral transmukosal och 1,16 ng/ml för subkutan administrering. Medianvärden för AUC var 41 ng·h/ml för oral transmukosal och 337 ng·h/ml för subkutan administrering. Smärtpoängen från RbtGs samt subjektiv bedömning var väl korrelerade efter både oral transmukosal och subkutan administration (ρ = 0,94 respektive ρ=0,90). Smärtpoängen korrelerade inte med plasmakoncentrationer av buprenorfin. Smärtpoängen från RbtGs vid oral transmukosal administrering var signifikant högre (p < 0.05) vid endast en tidpunkt (15 minuter) av totalt åtta jämfört med subkutan administrering. Sammanfattningsvis kan ingen av administrationssätten anses tillförlitliga med ledning av den stora variationen i plasmakoncentrationer av buprenorfin. Buprenorfin absorberades inte like väl efter oral transmukosal som subkutan administration, givet plasmakoncentrationerna. Fler studier behövs för att konfirmera dessa fynd och för att hitta djurägarvänliga alternativ för smärtbehandling i hemmet. SLU/Dept. of Clinical Sciences (until 231231) 2016 H3 eng swe https://stud.epsilon.slu.se/9518/ |
| spellingShingle | rabbit buprenorphine oral transmucosal subcutaneous drug administration analgesia pain scoring Freijs, Emma Comparison of plasma levels and analgesic effect between oral transmucosal and subcutaneous administration of buprenorphine in rabbits |
| title | Comparison of plasma levels and analgesic effect between oral transmucosal and subcutaneous administration of buprenorphine in rabbits |
| title_full | Comparison of plasma levels and analgesic effect between oral transmucosal and subcutaneous administration of buprenorphine in rabbits |
| title_fullStr | Comparison of plasma levels and analgesic effect between oral transmucosal and subcutaneous administration of buprenorphine in rabbits |
| title_full_unstemmed | Comparison of plasma levels and analgesic effect between oral transmucosal and subcutaneous administration of buprenorphine in rabbits |
| title_short | Comparison of plasma levels and analgesic effect between oral transmucosal and subcutaneous administration of buprenorphine in rabbits |
| title_sort | comparison of plasma levels and analgesic effect between oral transmucosal and subcutaneous administration of buprenorphine in rabbits |
| topic | rabbit buprenorphine oral transmucosal subcutaneous drug administration analgesia pain scoring |