注射用鼠抗人T淋巴细胞CD25抗原单克隆抗体在健康受试者体内药代动力学与药效学  

Pharmacokinetics and pharmacodynamics of monoclonal antibody of mouse anti-human T lymphocytes CD25 antigen in healthy Chinese volunteers

作　　者：方凯[1] 黎维勇[1] 马林[1] 李茜[1] 乔建[1] 邓俊刚[1] 张爱华[2] 张囡[2] 孙可芳[2] 

机构地区：[1]华中科技大学同济医学院附属协和医院,武汉430022 [2]武汉生物制品研究所,武汉430060

出　　处：《中国临床药理学杂志》2011年第6期439-442,共4页The Chinese Journal of Clinical Pharmacology

摘　　要：目的研究注射用鼠抗人T淋巴细胞CD25抗原单克隆抗体(WuTac)单次给药在中国健康受试者体内的药代动力学特征和药效学效应。方法 36名健康受试者,男女各半,随机分配到高,中,低(0.20,0.10,0.05 mg.kg-1)3个剂量组,通过酶联免疫吸附(ELISA)检测受试者血清中WuTac和人抗鼠抗体(HAMA)的浓度,评估该药物的药代动力学行为特征。通过流式细胞仪检测全血中T淋巴细胞表面CD25结合位点,计算白介-2受体(IL-2R)饱和度,对本品的药效学做出评判。结果高,中,低3个剂量组的主要药代动力学参数如下:t1/2分别为(54.15±16.50),(54.39±21.17),(43.99±13.07)h;tmax分别为(2.50±2.02),(2.75±2.01),(2.08±2.06)h;Cmax分别为(2950.82±560.94),(1461.20±370.70),(608.95±81.66)μg·L-1;AUC0-t分别为(8881.90±2188.10),(3711.00±1146.10),(1158.20±306.20)μg·L-1.d;AUC0-∞分别为(9458.80±2547.80),(4115.40±1208.40),(1269.70±310.40)μg·L-1.d。高,中,低3个剂量组单次恒速滴注停药1 h后,均能饱和T细胞白介2受体(IL-2R)相应结合位点,饱和度达96%以上,维持饱和3 d以上。结论本品在中国健康人体起效迅速,疗效持久。单次给药耐受性良好,呈线性药代动力学特征。Objective To study the pharmacokinetics and pharmacodynamics of monoclonal antibody of mouse anti-human T lymphocytes CD25 antigen（WuTac） in healthy Chinese subjects after single intravenous infusion.Methods The concentration of WuTac and human antimouse antibody（HAMA） in human plasma was determined to estimate the pharmacokinetic characteristics by the utilization of enzyme linked immunosorbent assay metnod（ELISA）.The saturation of interleukin-2 recepter（IL-2R） on T lymphocyte was detected to evaluate the pharmacodynamic features using flow cytometer.Results The pharmacokinetic paramaters in three groups of high,middle,low dose levels are as follows： t1/2 were（54.15±16.50）,（54.39± 21.17）,（43.99± 13.07） h;tmax were（2.50±2.02）,（2.75±2.01）,（2.08±2.06）h;Cmax were（2950.82±560.94）,（1461.20±370.70）,（608.95±81.66）μg·L-1;AUC0-t were（8881.90±2188.10）,（3711.00±1146.10）,（1158.20±306.20）μg·L-1·d;AUC0-∞were（9458.80±2547.80）,（4115.40±1208.40）,（1269.70±310.40） μg·L-1·d,respectively. The saturation of IL-2R on T lymphocyte was more than 96% 1 h after the infusion,and it maintained for more than 3 days.Conclusion WuTac exerted effect quickly,it was well tolerated,and showed linear pharmacokinetic characteritics.

关 键 词：人抗鼠抗体 白介2受体 酶联免疫吸附 药代动力学 药效学 

分 类 号：R969.1[医药卫生—药理学] R979.5[医药卫生—药学]