注射用鼠抗人T淋巴细胞CD25抗原单克隆抗体在肾移植患者体内的药动学与药效学

Pharmacokinetics and pharmacodynamics of monoclonal antibody of mouse anti-human T lymphocytes CD25 antigen in renal transplantation recipients

目的研究注射用鼠抗人T淋巴细胞CD25抗原单克隆抗体(WuTac)在肾移植患者体内的药动学和药效学。方法 16名肾移植患者随机分配到低、高(0.2,0.1 mg.kg-1)2个剂量组,用酶联免疫吸附法检测受试者血清中WuTac和人抗鼠抗体(HAMA)的浓度,评估该药物的药动学行为特征;通过流式细胞仪,检测全血中T细胞表面CD25结合情况,评判其药效学。结果低、高2个剂量组的主要药动学参数:T1/2分别为(51.41±16.24)(,59.53±24.96)h;AUCss分别为(2.28±0.35)(,5.13±1.53)mg.d.L-1;AUC0-t分别为(8.63±1.87)(,19.16±9.01)mg.d.L-1;AUC0-∞分别为(9.11±2.28)(,21.03±10.88)mg.d.L-1;Cmax分别为(3.27±0.53)(,8.36±1.92)mg.L-1;Tmax分别为(2.50±0.76)(,2.47±1.06)h。2组多次恒速滴注停药后,均能饱和T细胞白介2受体(IL-2R)相应结合位点。结论本品在中国肾移植患者起效迅速,疗效持久。多次给药耐受性良好,WuTac在0.1～0.2 mg.kg-1内基本呈线性药动学特征。

Objective To study the pharmacokinetics and pharmacodynamics of monoclonal antibody of mouse anti-human T lymphocytes CD25 antigen（WuTac） in renal transplantation recipients after multiple 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 method.The pharmacodynamic features was evaluated using flow cytometer.Results The pharmacokinetic paramaters in two groups of low and high dose were as follows： T1/2 are（51.41±16.24）,（59.53±24.96） h;AUCss are（2.28±0.35）,（5.13±1.53） mg·d·L^-1;AUC0-t are（8.63±1.87）,（19.16±9.01） mg·d·L^-1;AUC0-∞ are（9.11±2.28）,（21.03±10.88） mg·d·L^-1;Cmax are（3.27±0.53）,（8.36±1.92） mg·L^-1;Tmax are（2.50±0.76）,（2.47±1.06） h,respectively.Conclusion WuTac quickly,it was well tolerated,and showed linear pharmacokinetic characteristics in dose of 0.1-0.2 mg·kg^-1.