Moran Caileen R, Park Thomas J, Buffenstein Rochelle, Chakrabarty Sayan, Lindeblad Matthew O, Fortman Jeffrey D, Adams Cynthia R
Post-doctoral Training Program, University of Illinois Chicago, Chicago, Illinois.
Department of Biological Sciences, University of Illinois Chicago, Chicago, Illinois.
J Am Assoc Lab Anim Sci. 2024 Jul 30;63(5):565-71. doi: 10.30802/AALAS-JAALAS-24-045.
Unique characteristics of the naked mole-rat (NMR) have made it increasingly popular as a laboratory animal model. These rodents are used to study many fields of research including longevity and aging, cancer, circadian rhythm, pain, and metabolism. Currently, the analgesic dosing regimens used in the NMR mirror those used in other rodent species. However, there is no pharmacokinetic (PK) data supporting the use of injectable analgesics in the NMR. Therefore, we conducted 2 independent PK studies to evaluate 2 commonly used analgesics in the NMR: meloxicam (2 mg/kg SC) and buprenorphine (0.1 mg/kg SC). In each study, blood was collected at 8 time points after subcutaneous injection of meloxicam or buprenorphine (0 [predose], 0.25, 0.5, 1, 2, 4, 8, and 24 h). Three NMRs were used per time point for a total of 24 animals per PK study. Plasma concentrations of meloxicam were highest between 0.5 and 1 h postinjection. Levels remained above the extrapolated dog and cat therapeutic threshold levels (390 to 911 ng/mL) for at least 24 h. Plasma concentrations of buprenorphine were highest between 0.25 and 0.5 h postinjection. Levels remained above the human therapeutic threshold (1 ng/mL) for up to 21 h. No skin reactions were seen in association with injection of either drug. In summary, these data support dosing meloxicam (2 mg/kg SC) once every 24 h and buprenorphine (0.1 mg/kg SC) once every 8 to 12 h in the NMR. Further studies should be performed to evaluate the clinical efficacy of these drugs by correlating plasma concentrations with postoperative pain assessments.
裸鼹鼠(NMR)的独特特性使其作为实验动物模型越来越受欢迎。这些啮齿动物被用于研究包括长寿与衰老、癌症、昼夜节律、疼痛和新陈代谢等许多研究领域。目前,裸鼹鼠中使用的镇痛给药方案与其他啮齿动物物种中使用的方案相似。然而,尚无药代动力学(PK)数据支持在裸鼹鼠中使用注射用镇痛药。因此,我们进行了两项独立的PK研究,以评估裸鼹鼠中两种常用的镇痛药:美洛昔康(2mg/kg皮下注射)和丁丙诺啡(0.1mg/kg皮下注射)。在每项研究中,皮下注射美洛昔康或丁丙诺啡后,在8个时间点(0[给药前]、0.25、0.5、1、2、4、8和24小时)采集血液。每个时间点使用3只裸鼹鼠,每项PK研究总共使用24只动物。美洛昔康的血浆浓度在注射后0.5至1小时之间最高。这些水平至少在24小时内保持高于外推的犬和猫治疗阈值水平(390至911ng/mL)。丁丙诺啡的血浆浓度在注射后0.25至0.5小时之间最高。这些水平在长达21小时内保持高于人类治疗阈值(1ng/mL)。注射这两种药物均未观察到皮肤反应。总之,这些数据支持在裸鼹鼠中每24小时皮下注射一次美洛昔康(2mg/kg),每8至12小时皮下注射一次丁丙诺啡(0.1mg/kg)。应进行进一步研究,通过将血浆浓度与术后疼痛评估相关联来评估这些药物的临床疗效。