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

Abstract

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 (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). 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.

Physiologically based pharmacokinetic modelling of semaglutide in children and adolescents with healthy and obese body weights

“…It is feasible that the amount of SC fat influences the absorption rate due to less vascularization of adipose tissue. The increased skinfold thickness as well as higher BMI has also been associated with delayed absorption of SC administered drugs 54,80–82 …”

“…The increased skinfold thickness as well as higher BMI has also been associated with delayed absorption of SC administered drugs. 54,[80][81][82] Further, the P-PBPK models were used to predict the dose adjustments for 10-14-year-old children with healthy body weights. For the 10-12-year-old adolescent simulations, 0.25 mg twice weekly dosing for semaglutide would be the preferred indication (Tables 9 and 10).…”

Intramuscular alfaxalone with or without buprenorphine or hydromorphone provides sedation with minimal adverse effects in healthy rabbits (Oryctolagus cuniculus) in a randomized blinded controlled trial

“…12,17 Effective analgesia is more likely to be achieved following IM or IV administration due to higher blood plasma levels obtained with these routes. 18 Hydromorphone is a full μ-opioid receptor agonist used to treat moderate to severe pain. Its administration provides analgesia but may also result in mild to moderate sedation in dogs and cats.…”

Pharmacokinetics and Pharmacodynamics of Butorphanol and Dexmedetomidine after Intranasal Administration in Broiler Chickens (Gallus gallus domesticus)

“…Inappropriate injections into thigh muscles could cause nerve damage, and there is a risk of excretion of the injected drug before its absorption due to activation renal portal system controlled by autonomic nervous system in birds [ 4 ]. The absorption of drugs after subcutaneous (SC) injection can be slower as compared to intravenous (IV) administration, resulting in slower onset of action [ 5 ]. Previous studies in birds demonstrated that several classes of sedative–analgesics, such as benzodiazepines, opioids and alpha 2 agonists, are effective when administered intranasally [ 6 , 7 , 8 ].…”