Pharmacokinetics, Fecal Output, and Grimace Scores in Rabbits Given Long-acting Buprenorphine or Fentanyl for Postsurgical Analgesia.

The New Zealand white rabbit (Oryctolagus cuniculus) is a frequently used surgical model. Pain management after surgery is a critical aspect of animal welfare. Recently, a long-acting buprenorphine formulation (Ethiqa XR; EXR) was approved for use in rats and mice but has not yet been investigated in rabbits. The current study aimed to determine whether a single subcutaneous dose of 0.15mg/kg of EXR could achieve and maintain therapeutic buprenorphine plasma concentrations (0.1ng/mL) for 72h in male and female rabbits. We also evaluated the safety profiles of EXR and the fentanyl patch (FP) by assessing fecal output after surgery, because opioids are known to decrease intestinal motility. Behavior and pain scores were compared for rabbits that received either EXR or the FP after undergoing an annulus puncture procedure to induce osteoarthritis. EXR at 0.15mg/kg SC provided a shorter time to onset and sustained analgesia for 72h in male and female rabbits, whereas the FP provided suboptimal analgesia after 48h. Both EXR and FP reduced fecal output after surgery. Output returned to baseline levels within 72h for the EXR group and remained slightly below baseline at 96h after surgery for the fentanyl group. Grimace pain scores revealed no significant difference between treatment groups. These results suggest that EXR is a safe and effective option for postoperative pain management in rabbits.

Comparative Pharmacokinetics and Injection Site Histopathology in Nude Mice Treated with Long-acting Buprenorphine Formulations.

Two long-acting formulations of buprenorphine are commercially available as analgesics for rodents. However, these drugs have not yet been studied in nude mice. We sought to investigate whether the manufacturer-recommended or labeled mouse doses of either drug would provide and sustain the purported therapeutic plasma concentration of buprenorphine (1 ng/mL) over 72 h in nude mice and to characterize the injection site histopathology. NU/NU nude and NU/+ heterozygous mice were subcutaneously injected with extended-release buprenorphine polymeric formulation (ER; 1 mg/kg), extendedrelease buprenorphine suspension (XR; 3.25 mg/kg), or saline (2.5 mL/kg). Plasma concentrations of buprenorphine were measured 6, 24, 48, and 72 h after injection. The injection site was examined histologically at 96 h after administration. XR dosing yielded significantly higher plasma buprenorphine concentrations than did ER dosing at every time point in both nude and heterozygous mice. No significant difference in plasma buprenorphine concentrations were detected between nude and heterozygous mice. Both formulations yielded plasma levels of buprenorphine of over 1 ng/mL at 6 h; XR sustained buprenorphine plasma levels above 1 ng/mL for over 48 h, whereas ER sustained this level for over 6 h. Injections sites of both formulations were characterized by a cystic lesion with a fibrous/fibroblastic capsule. ER induced more inflammatory infiltrates than did XR. This study indicates that while both XR and ER are suitable for use in nude mice, XR has a longer duration of likely therapeutic plasma levels and induces less subcutaneous inflammation at the injection site.