Guarnieri Michael, Brayton Cory, Tyler Betty M
Johns Hopkins School of Medicine, Department of Neurological Surgery, Baltimore, MD, USA.
Johns Hopkins School of Medicine, Department of Molecular and Comparative Pathobiology, Baltimore, MD, USA.
J Vet Med. 2018 Jul 9;2018:2616152. doi: 10.1155/2018/2616152. eCollection 2018.
Animal models to study opiates are of growing interest. We have examined the short-term safety of buprenorphine implants in Fischer F344/NTac rats treated with excess doses of a cholesterol-triglyceride suspension of buprenorphine. A single injection of 0.65 mg/kg afforded clinically significant blood levels of analgesia for 3 days. Chemistry, hematology, coagulation, and urinalysis values with 2- to 10-fold excess doses of the drug-lipid suspension were within normal limits. Histopathology findings were unremarkable. The skin and underlying tissue surrounding the drug injection were unremarkable. Here we report the results of a long-term follow-up study of female rats injected with 0.65 and 1.3 mg/kg. The 14-month evaluation showed no abnormal findings that could be attributed to the drug or lipid suspension. These results confirm the safety of cholesterol-triglyceride carrier systems for subcutaneous drug delivery in laboratory animals and suggest that this model may be used to study long-term effects of opiate therapy.
用于研究阿片类药物的动物模型越来越受到关注。我们研究了用过量布托啡诺胆固醇 - 甘油三酯混悬液处理的Fischer F344/NTac大鼠中布托啡诺植入剂的短期安全性。单次注射0.65mg/kg可使血液中的镇痛水平在临床上显著维持3天。使用2至10倍过量剂量的药物 - 脂质混悬液时，化学、血液学、凝血和尿液分析值均在正常范围内。组织病理学检查结果无异常。药物注射部位周围的皮肤和皮下组织无异常。在此我们报告对注射了0.65mg/kg和1.3mg/kg的雌性大鼠进行长期随访研究的结果。14个月的评估显示没有可归因于药物或脂质混悬液的异常发现。这些结果证实了胆固醇 - 甘油三酯载体系统在实验动物皮下给药的安全性，并表明该模型可用于研究阿片类药物治疗的长期效果。
