Comparison of plasma levels and analgesic effect between oral transmucosal and subcutaneous administration of buprenorphine in rabbits

Sammanfattning: 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.