重组抗肿瘤坏死因子-α全人源单克隆抗体在食蟹猴体内的药代动力学研究  

Pharmacokinetics of recombinant fully human anti-tumor necrosis factor-α amonoclonal antibody in machin

作　　者：孙旭[1,2] 李佐刚[1] 闻镍[1] 熊玉卿[2] 

机构地区：[1]中国食品药品检定研究院国家药物安全评价监测中心,北京100176 [2]南昌大学医学院临床药理研究所,南昌330006

出　　处：《中国临床药理学杂志》2015年第7期532-535,共4页The Chinese Journal of Clinical Pharmacology

摘　　要：目的研究抗肿瘤坏死因子-α(TNF-α)全人源单抗在食蟹猴体内的药代动力学特征及生物利用度。方法 20只食蟹猴皮下或静脉给予1,3或10mg·kg-1抗TNF-α全人源单抗,用ELISA试剂盒测定食蟹猴血浆中抗TNF-α全人源单抗的含量,研究其给药后168 h内药代动力学特征与生物利用度。结果抗TNF-α全人源单抗皮下注射给药的低中高3个剂量分别为1,3,10mg·kg-1时,AUC0-168随着剂量的增大而增大(P<0.05),而t1/2、Vz/F、Cl/F均不随剂量而改变(P>0.05)。比较中剂量的皮下与静脉2种给药方式,结果抗TNF-α全人源单抗皮下给药的生物利用度为77.5%。结论在本实验的给药浓度范围内,且在给药后168 h内,抗TNF-α全人源单抗在食蟹猴血浆中的暴露呈线性药代动力学特征,且皮下给药生物利用度较高,体内吸收良好。Objective To investigate the pharmacokineics and bioavai-lability of recombinant fully human anti -tumor necrosis factor -α（ TNF-α） amonoclonal monoclonal antibody. Method Twenty machins were subcutaneous or intravenous given fully human anti -TNF-αamonoclonal monoclonal antibody （1, 3 or 10 mg· kg -1 ）.By using the validated enzyme -linked immuno sorbent assay （ ELISA ） kits for the determination of content of fully human anti -TNF-αamono-clonal monoclonal antibody in the plasma of machines , in order to study the pharmacokineics within 168 h and bioavailability.Result After the subcutaneous administration of 1, 3 and 10 mg· kg -1 of fully human anti-TNF-αamonoclonal monoclonal antibody injection , the AUC0-168 in-creased （ P〈0.05 ） , but not the t1/2 , Vz/F, CL/F increased with the dose.The bioavailability of fully human anti -TNF -αamonoclonal monoclonal antibody after subcutaneous administration was 77.5%.Con-clusion In the range of administration concentration of this study , the plasma exposure of fully human anti -TNF-αamonoclonal monoclonal antibody had a linear pharmacokinetic profile in machin within 168 h after administration.Fully human anti -TNF -αamonoclonal mono-clonal antibody was well absorbed with a high bioavability.

关 键 词：重组抗肿瘤坏死因子-α全人源单克隆抗体 食蟹猴 药代动力学 生物利用度 

分 类 号：R978[医药卫生—药品] R969.1[医药卫生—药学]