Unit for Laboratory Animal Medicine. University of Michigan, Ann Arbor, Michigan;, Email:
Unit for Laboratory Animal Medicine. University of Michigan, Ann Arbor, Michigan.
J Am Assoc Lab Anim Sci. 2022 Jul 1;61(4):381-387. doi: 10.30802/AALAS-JAALAS-22-000021. Epub 2022 Jul 8.
Buprenorphine is commonly used to control postoperative pain in rodents. Short-acting formulations of buprenorphine (bup-HCl) require frequent handling and restraint of animals for appropriate dosing, which can be stressful and confound research outcomes. Ethiqa XR (bup-ER) is an FDA-indexed extended-release buprenorphine formulation that is an alternative to bup-HCl in mice and rats. In the current study, we first evaluated the pharmacokinetics of bup-ER in male C57BL/6J mice by sampling blood at 10 time points, ranging from 30 min to 72 h after administration ( = 3 mice per time point). Average plasma concentrations fell below therapeutic levels at 48 h after administration. We also evaluated the safety of bup-ER when administered prior to surgery in combination with common anesthetics and the efficacy of bup-ER in mouse laparotomy. Anesthetic safety was studied by measuring respiratory rate, rectal temperature, and recovery time in groups of mice ( = 8) given bup-HCl, bup-ER, or saline in combination with isoflurane or ketamine-xylazine anesthesia. No differences were seen between analgesic treatment groups with either of the general anesthetics. To evaluate efficacy, mice ( = 10) were randomly allocated to receive either bup-ER (3.25 mg/kg) once presurgically, bup-HCl (0.1 mg/kg) presurgically and then every 8 h, or saline once before surgery. Mice underwent a sham laparotomy and were assessed for pain based on changes in weight, cageside ethogram, nesting consolidation test, rearing frequency, and nociception to von Frey testing at 6, 12, 24, 48, and 72 h after surgery. Cageside ethogram, rearing frequency, and von Frey testing showed significant differences between bup-ER-treated mice and saline controls in the early postoperative period. No significant effects between treatment groups were seen in daily weights or nesting consolidation scores. This study demonstrates that bup-ER can be safely administered before surgery and provides analgesia for up to 48 h after administration based on pharmacokinetic and behavioral data.
丁丙诺啡常用于控制啮齿动物的术后疼痛。丁丙诺啡的短效制剂（丁丙诺啡盐酸盐）需要频繁处理和限制动物以进行适当的剂量，这可能会带来压力并影响研究结果。Ethiqa XR（丁丙诺啡 ER）是一种 FDA 索引的延长释放丁丙诺啡制剂，是小鼠和大鼠中丁丙诺啡盐酸盐的替代品。在本研究中，我们首先通过在给药后 10 个时间点（每个时间点 3 只小鼠）采集血液，评估了雄性 C57BL/6J 小鼠中丁丙诺啡 ER 的药代动力学。给药后 48 小时平均血浆浓度降至治疗水平以下。我们还评估了在手术前与常用麻醉剂联合使用丁丙诺啡 ER 的安全性，并评估了丁丙诺啡 ER 在小鼠剖腹手术中的疗效。通过测量呼吸频率、直肠温度和麻醉后恢复时间，研究了丁丙诺啡盐酸盐、丁丙诺啡 ER 或生理盐水与异氟烷或氯胺酮-甲苯噻嗪麻醉联合使用的麻醉安全性。在两种全身麻醉剂中，镇痛治疗组之间没有差异。为了评估疗效，将小鼠（每组 10 只）随机分为术前接受丁丙诺啡 ER（3.25 mg/kg）、术前接受丁丙诺啡盐酸盐（0.1 mg/kg）然后每 8 小时一次、或术前一次生理盐水。小鼠接受假剖腹手术，并根据手术后 6、12、24、48 和 72 小时体重变化、笼边行为表、筑巢巩固测试、饲养频率和von Frey 测试评估疼痛。笼边行为表、饲养频率和 von Frey 测试显示，在术后早期，丁丙诺啡 ER 治疗的小鼠与生理盐水对照组之间存在显著差异。在每日体重或筑巢巩固评分方面，治疗组之间没有显著差异。这项研究表明，丁丙诺啡 ER 可以在手术前安全使用，并根据药代动力学和行为数据在给药后长达 48 小时提供镇痛作用。
