Pharmacokinetics of Extended-release Buprenorphine in Mongolian Gerbils (Meriones unguiculatus).

Aleaya R Bowie, Katherine N Gibson-Corley, Erin Nz Yu
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Abstract

Both the Guide for the Care and Use of Laboratory Animals and the Animal Welfare Act and Regulations require animals in research to receive adequate analgesia unless an exception can be scientifically justified and IACUC approved. Extended- release buprenorphine (BUP-XR) is a pharmaceutical-grade formulation that is FDA-indexed for use in mice and rats. However, this new formulation has not been evaluated in adult Mongolian gerbils (Meriones unguiculatus). Our goal was to determine whether the extrapolated dose (1 mg/kg SC) would achieve plasma buprenorphine concentrations above the murine therapeutic threshold (> 1.0 ng/mL) in male and female gerbils. We hypothesized that BUP-XR administered at 1 mg/kg would achieve the murine therapeutic threshold in both male and female gerbils until at least 48 h after injection. Gerbils received one injection of BUP-XR (1 mg/kg SC) and underwent 4 serial blood collections (0.5, 1, 2, and 4, or 0.5, 24, 48, and 72 h after injection). The average plasma buprenorphine concentrations were above 1 ng/mL within 30 min of administration for both males and females. Plasma buprenorphine concentrations remained above 1.0 ng/mL for 48 h after administration. In males, plasma buprenorphine concentrations were significantly higher at 1 h after injection as compared with females; no other significant differences were observed between sexes. Mild to moderate injection-site granulomas were observed in five of nine gerbils, presumably due to the lipid matrix of the BUP-XR formulation. Our findings demonstrate that a single BUP-XR dose (1 mg/kg SC) achieves plasma buprenorphine levels that remain above the murine therapeutic threshold of 1.0 ng/mL for up to 48 h in both sexes.

丁丙诺啡缓释制剂在蒙古沙鼠体内的药代动力学。
《实验动物护理和使用指南》和《动物福利法和条例》都要求动物研究必须接受足够的镇痛,除非有科学依据和IACUC批准的例外情况。丁丙诺啡(BUP-XR)是一种药物级制剂,经美国食品药品监督管理局(FDA)索引,可用于小鼠和大鼠。然而,这种新配方尚未在成年蒙古沙鼠(有爪沙鼠)中进行评估。我们的目标是确定推断剂量(1 mg/kg SC)是否能使雄性和雌性沙鼠的血浆丁丙诺啡浓度高于尿液治疗阈值(>1.0 ng/mL)。我们假设,在雄性和雌性沙鼠中,以1mg/kg给药的BUP-XR将达到小鼠治疗阈值,直到注射后至少48小时。Gerbil接受了一次BUP-XR(1 mg/kg SC)注射,并进行了4次连续采血(注射后0.5、1、2和4小时,或0.5、24、48和72小时)。雄性和雌性的平均血浆丁丙诺啡浓度在给药30分钟内均高于1 ng/mL。给药后48小时,血浆丁丙诺啡浓度保持在1.0 ng/mL以上。在男性中,注射后1小时血浆丁丙诺啡浓度显著高于女性;性别之间没有观察到其他显著差异。在9只沙鼠体内观察到轻度至中度注射部位肉芽肿,可能是由于BUP-XR制剂的脂质基质所致。我们的研究结果表明,单次BUP XR剂量(1 mg/kg SC)可使血浆丁丙诺啡水平在两性中保持在1.0 ng/mL的小鼠治疗阈值以上长达48小时。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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