两种重组抗蓖麻毒素人源化单克隆抗体制剂在猕猴体内的药代动力学研究  

Pharmacokinetics of two recombinant humanized monoclonal antibodies against ricin in rhesus monkeys

作　　者：高雅 朱晓霞 孟志云 甘慧 顾若兰 吴卓娜 孙文种 窦桂芳 GAO Ya;ZHU Xiao-xia;MENG Zhi-yun;GAN Hui;GU Ruo-lan;WU Zhuo-na;SUN Wen-zhong;DOU Gui-fang(Institute of Radiation Medicine,Academy of Military Medical Sciences,Beijing 100850,China)

机构地区：[1]军事医学研究院辐射医学研究所,北京100850

出　　处：《药学学报》2022年第2期480-483,共4页Acta Pharmaceutica Sinica

摘　　要：重组抗蓖麻毒素人源化单克隆抗体(MIL50)是针对蓖麻毒素靶点的重组人源化单克隆抗体。本文利用ELISA的方法建立猕猴血清中MIL50的测定方法,并运用交叉设计方法,将12只猕猴先后单次静脉推注1 mg·kg^(-1)受试制剂(MIL50冻干粉剂)和参比制剂(MIL50液体制剂),测定不同时间点MIL50血药浓度,并进行相关药动学参数分析,比较MIL50液体制剂与冻干粉剂在猕猴体内中的药代动力学特征,动物福利和实验过程均遵循军事医学科学院动物伦理委员会的规定,以及军事医学研究院辐射研究所动物实验和福利委员会制定的法规(IACUC-DWZX-2020-503)。结果显示,两组C_(max)与AUC_(0-5d)差异没有统计学意义;液体制剂为参比制剂,C_(max)比值为101.6%,AUC_(0-5d)比值为101.9%;C_(max)的90%可信区间为79.42%~129.92%,AUC_(0-5d)的90%可信区间为85.72%~121.18%。这提示不同剂型MIL50在猕猴体内血药浓度变化有一定差异。Recombinant humanized anti-ricin monoclonal antibody(MIL50)is a recombinant humanized monoclonal antibody targeting ricin.In this study,an ELISA method was used to establish a method for the determination of MIL50 in macaque serum,and a cross design method was used.Twelve rhesus monkeys were intravenously injected 1 mg·kg^(-1) test preparation(MIL50 freeze-died powder injection)and reference preparation(MIL50 liquid preparation)to determine the plasma concentration of MIL50 at different time points,and the pharmacokinetic parameters were analyzed to compare the pharmacokinetic characteristics of MIL50 liquid preparation and freeze-died powder injection in rhesus monkeys.Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of the Chinese Academy of Medical Sciences and Use of Laboratory Animals and the regulations derived by the Animal Care and Welfare Committee of the Institute of Radiation Medicine,Academy of Military Medical Sciences(IACUC-DWZX-2020-503).The results showed that there was no significant difference between C_(max) and AUC_(0-5d) in the two groups.The liquid preparation was the reference preparation,with C_(max) ratio of 101.6% and AUC_(0-5d) ratio of 101.9%,the 90% confidence interval of C_(max) was 79.42%-129.92%,and the 90% confidence interval of AUC_(0-5d) was 85.72%-121.18%.These results suggested that different dosage forms of MIL50 had certain differences in the changes of blood drug concentration in rhesus monkeys.

关 键 词：蓖麻毒素 重组抗蓖麻毒素人源化单克隆抗体 药代动力学 液体制剂 冻干粉剂 

分 类 号：R965[医药卫生—药理学]