锝[^(99m)Tc]喷替酸盐注射液单次给药毒性和局部毒性研究  

Study on the Single Dose Toxicity and Local Toxicity of Technetium [^(99m)Tc]Pentetate Acid Injection

作　　者：高洁 张伟[1] 李梅[1] 孙鸽[1] 胡波[2] 王若琪 靳洪涛[3] 李建国[1] GAO Jie;ZHANG Wei;LI Mei;SUN Ge;HU Bo;WANG Ruoqi;JIN Hongtao;LI Jianguo(Drug Safety Evaluation Center in China Institute for Radiation Protection;Shanxi Key Laboratory of Drug Toxicology and Drug for Radiation Injury,Division of Radiology and Environmental Medicine of China Institute for Radiation Protection,Shanxi Taiyuan 030006,China;Irradiation Technology Factory,Shanxi Taiyuan 030006,China;Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China)

机构地区：[1]中国辐射防护研究院药物安全性评价中心/药物毒理与放射损伤药物山西省重点实验室/中国辐射防护研究院放射医学与环境医学研究所,山西太原030006 [2]中国辐射防护研究院辐照技术中心,山西太原030006 [3]中国医学科学院药物研究所,北京100050

出　　处：《中国药物警戒》2019年第1期18-22,共5页Chinese Journal of Pharmacovigilance

基　　金：国防科工局核能开发项目:放射性药物安全性评价关键技术研究;中国辐射防护研究院院基金项目:放射性药物安全评价研究;山西省科技基础条件平台项目(201805D141007)

摘　　要：目的探讨锝[^(99m)Tc]喷替酸盐注射液临床前安全性,为后续放射性药物安全性研究提供参考。方法选取ICR小鼠、新西兰兔和豚鼠,分别开展尾静脉注射单次给药毒性实验(对照组、5 550 MBq·kg^(-1)组和925 MBq·kg^(-1)组),血管刺激、肌肉刺激和主动全身过敏试验。实验期间观察动物状态,测定动物体重、饲料消耗量并进行组织病理学检查,其中单次给药实验检测血液学指标,对死亡动物及观察期结束后仍存活动物进行大体解剖检查,摘取胸腺、脾脏、肾脏、睾丸称重,计算脏器系数。结果单次给药实验5 550 MBq·kg^(-1)组动物给药后均眼睑下垂,静卧少动,给药后约10 min有1只雄性动物死亡;925 MBq·kg^(-1)组动物未见明显异常。血管刺激、肌肉刺激和主动全身过敏试验给药组均未见明显异常。结论本实验条件下未发现与药物有关的明显毒性反应,为其临床安全应用提供了参考信息。Objective To study the preclinical safety of technetium[99mTc]pentetate acid injection,so as to provide a reference for the safety study of radiopharmaceuticals.Methods ICR mice,New Zealand rabbits and guinea pigs were used respectively to carry out the single dose toxicity test of tail intravenous injection(control group,5 550 MBq·kg-1 group and 925 MBq·kg^-1 group),vein irritating test,muscle irritating test and active systemic anaphylaxis test.The general symptoms were observed,while the weight changes of the animals and the feed consumption were determined during tests.Histopathological examination was performed,in which hematological indexes were detected by single dose toxicity,gross anatomy examination was performed on dead animals and animals still alive after the end of observation period,thymus,spleen,kidney and testicles were extracted for weighing,and viscera coefficients were calculated.Results All the mice in the 5 550 MBq·kg^-1 group had drooping eyelids and little movement after administration,and one male animal died about 10 min after administration.No obvious abnormality was found in animals in the 925 MBq·kg^-1 group.Vein irritating,muscle irritating and active systemic anaphylaxis group showed no obvious abnormalities.Conclusion No obvious toxic reaction related to the drug was found under the conditions of this experiment,suggesting that it provides reference information for its clinical safe application.

关 键 词：99mTc 单次给药毒性 局部毒性 安全性评价 放射性药物 

分 类 号：R981[医药卫生—药品]