DeTolla L, Sanchez R, Khan E, Tyler B, Guarnieri M
Departments of Pathology, Medicine, Epidemiology and Public Health and the Program of Comparative Medicine, School of Medicine, University of Maryland, Baltimore, MD, USA.
Program of Comparative Medicine, School of Medicine, University of Maryland, Baltimore, MD, USA.
J Vet Med. 2014;2014:365673. doi: 10.1155/2014/365673. Epub 2014 Nov 27.
Subcutaneous drug implants are convenient systems for the long-term delivery of drugs in animals. Lipid carriers are logical tools because they generally allow for higher doses and low toxicity. The present study used an US Food and Drug Administration Target Animal Safety test system to evaluate the safety of a subcutaneous implant of a cholesterol-triglyceride-buprenorphine powder in 120 BALB/c mice. Mice were evaluated in 4- and 12-day trials with 1- and 5-fold doses of the intended 3 mg/kg dose of drug. One male mouse treated with three 3 mg/kg doses and surgery on days 0, 4, and 8 died on day 9. The cause of death was not determined. In the surviving 119 mice there was no evidence of skin reaction at the site of the implant. Compared to control animals treated with saline, weight measurements, clinical pathology, histopathology, and clinical observations were unremarkable. These results demonstrate that the lipid carrier is substantially safe. Cholesterol-triglyceride-drug powders may provide a valuable research tool for studies of analgesic and inflammatory drug implants in veterinary medicine.
皮下药物植入物是在动物体内长期给药的便捷系统。脂质载体是合理的工具，因为它们通常允许更高的剂量且毒性较低。本研究使用美国食品药品监督管理局的靶动物安全测试系统，评估了120只BALB/c小鼠皮下植入胆固醇-甘油三酯-丁丙诺啡粉末的安全性。在4天和12天的试验中，用预期3mg/kg剂量的1倍和5倍剂量对小鼠进行评估。一只在第0天、第4天和第8天接受三次3mg/kg剂量治疗并进行手术的雄性小鼠在第9天死亡。死亡原因未确定。在存活的119只小鼠中，植入部位没有皮肤反应的迹象。与用生理盐水治疗的对照动物相比，体重测量、临床病理学、组织病理学和临床观察均无异常。这些结果表明脂质载体基本安全。胆固醇-甘油三酯-药物粉末可能为兽医学中镇痛和抗炎药物植入物的研究提供有价值的研究工具。
