裸鼠注射用美洛昔康和丁丙诺啡的药代动力学。

Caileen R Moran, Thomas J Park, Rochelle Buffenstein, Sayan Chakrabarty, Matthew O Lindeblad, Jeffrey D Fortman, Cynthia R Adams
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引用次数: 0

摘要

裸鼹鼠(NMR)的独特特性使其成为越来越受欢迎的实验动物模型。这些啮齿动物被用于研究许多领域,包括长寿与衰老、癌症、昼夜节律、疼痛和新陈代谢。目前,在 NMR 中使用的镇痛剂剂量方案与在其他啮齿类动物中使用的剂量方案相同。然而,没有药代动力学 (PK) 数据支持在 NMR 中使用注射镇痛剂。因此,我们进行了两项独立的 PK 研究,以评估在 NMR 中常用的两种镇痛药:美洛昔康(2 毫克/千克 SC)和丁丙诺啡(0.1 毫克/千克 SC)。在每项研究中,在皮下注射美洛昔康或丁丙诺啡后的 8 个时间点(0 [用药前]、0.25、0.5、1、2、4、8 和 24 小时)采集血液。每个时间点使用三个 NMR,每次 PK 研究共使用 24 只动物。注射后 0.5 至 1 小时内,美洛昔康的血浆浓度最高。注射后 0.25 至 0.5 小时内,丁丙诺啡的血浆浓度最高。注射两种药物后均未见皮肤反应。总之,这些数据支持在 NMR 中每 24 小时注射一次美洛昔康(2 毫克/千克 SC)和每 8 至 12 小时注射一次丁丙诺啡(0.1 毫克/千克 SC)。应开展进一步研究,通过将血浆浓度与术后疼痛评估联系起来,评估这些药物的临床疗效。
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Pharmacokinetics of Injectable Meloxicam and Buprenorphine in the Naked Mole-Rat (Heterocephalus glaber).

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.

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