Comparative Safety and Efficacy of Extended-Release Buprenorphine Formulations for Mouse Reproductive Surgeries under Tribromoethanol.

Abstract

Extended-release buprenorphine formulations are commonly used to control postoperative pain in rodents with minimal handling-related stress. An FDA-indexed formulation is now available that has been demonstrated safe and effective with ketamine-xylazine and isoflurane anesthesia; however, safe use in combination with tribromoethanol, a nonpharmaceutical-grade anesthetic sometimes favored for short, high-volume procedures, has not been reported. Effects on pregnancy and offspring have also not been examined. In this study we compared the safety and efficacy of the FDA-indexed formulation at the labeled dose (3.25 mg/kg) to the compounded extended-release buprenorphine formulation used by the centralized Transgenic Core at our institution at the manufacturer-recommended dosage (1 mg/kg) in CD-1 mice under tribromoethanol anesthesia. A pilot (n = 5 females per drug) was initially conducted with anesthetic and analgesic in the absence of surgical manipulation, after which the formulations were compared in embryo transfer and vasectomy surgeries (n = 10 males or females per drug). Relative efficacy was assessed at 6, 24, 48, and 72 h after surgery using a cageside ethogram, frequency of rearing behavior compared with baseline, and weight change. No differences were seen between analgesic treatment groups. Safety was evaluated by intraoperative respiratory rate, recovery time, incidence of analgesic injection site lesions, and gross necropsy. Ulceration was only observed at the injection site of mice receiving compounded drug; no other differences between treatments were observed. Effects on pregnancy were evaluated by comparing pregnancy success, litter size, and pup weight at weaning between treatment groups in the initial experiment and embryo transfers subsequently performed by the Transgenic Core (n = 19 sets). No significant differences were identified. These results indicate that both formulations can be safely used in vasectomy and embryo transfer surgeries under tribromoethanol anesthesia; however, the FDA-indexed product may improve welfare by decreasing injection site ulceration compared with the compounded formulation.