注射用重组人CTLA4-抗体融合蛋白在健康人体的药动学  

Pharmacokinetics of the recombinant human cytotoxic T lymphocyte associate antigen-4 fusion protein for intravenous infusion in Chinese healthy volunteers

作　　者：邵威[1] 文爱东[1] 孙晓莉[2] 贾艳艳[1] 杨志福[1] 周敏[1] 

机构地区：[1]第四军医大学西京医院药剂科,西安710032 [2]第四军医大学药物化学教研室,西安710032

出　　处：《中国新药杂志》2008年第4期333-335,共3页Chinese Journal of New Drugs

摘　　要：目的：研究注射用重组人CTLA4-抗体融合蛋白（CTLA4-Ig）在中国健康人体内的药动学特征。方法：27例健康受试者随机分为1,10,20 mg·kg^-13个剂量组,每组9例,用酶联免疫吸附测定法（ELISA）测定人血清CTLA4-Ig浓度。结果：1,10,20 mg·kg^-13个剂量组Tmax均为0.0416 d;Cmax分别为（18.4±1.6）,（186.9±24.7）和（416.8±34.4）mg·L^-1,消除相半衰期t1/2分别为（15.13±2.62）,（14.21±2.35）和（11.77±1.24）d,AUC0-84 d分别为（171±28）,（1 490±231）和（2 977±362）mg·d·L^-1。结论：在1-20mg·kg^-1剂量范围内单次静脉滴注重组人CTLA4-抗体融合蛋白Cmax和AUC呈线性增长,与剂量呈正比。体内代谢呈线性代谢特征,与国外报道基本一致。Objective：To study the pharmacokinetics of a single intravenous infusion of recombinant human cytotoxic T lymphocyte associate antigen-4 fusion protein [ rhCTLA4-Ig] in Chinese healthy volunteers. Methods： Totally 27 healthy volunteers were randomly allocated into 3 groups （ n = 9 for each group） , and received intravenous infusion of rhCTLA4-Ig at 1, 10 and 20 mg· kg^-1, respectively. Serum CTLA4-Ig concentration was determined by enzyme linked immunosorbent assay. Results： The main pharmacokinetic parameters were as follows： T was all 0.041 6 d; Cmax were （18.4 ±1.6）, （186.9 ±24.7） and （416.8 ±34.4）mg· L^-1; t1/2 were （ 15.13 ± 2.62）, （ 14.21 ± 2.35 ） and （ 11.77 ±1.24） d; AUC0 -34 d were （ 171 ± 28 ）, （ 1 490 ± 231 ） and （2 977 ± 362） mg· d· L ^- 1. Conclusion ： After single intravenous infusion of rhCTLA4-Ig at 1 - 20 mg· kg ^-1, rhCT- LA4-Ig has the characteristics of linear pharmacokinetics.

关 键 词：重组人CTLA4-抗体融合蛋白 酶联免疫吸附测定法 药动学 

分 类 号：R969.1[医药卫生—药理学] R915.2[医药卫生—药学]