聚乙二醇重组人粒细胞集落刺激因子注射液Ⅰ期临床药代动力学和药效学研究  

A phase Ⅰ study to evaluate the clinical pharmacokinetics and pharmacodynamics of pegylated recombinant human granulocyte colony-stimulating factor

作　　者：韩晓红[1] 张春玲[1] 刘鹏[1] 宋媛媛[1] 姚嘉瑞[1] 秦燕[1] 唐乐[1] 张淑香[1] 李丹[1] 冯云[1] 石远凯[1] 

机构地区：[1]北京协和医学院中国医学科学院肿瘤医院肿瘤研究所内科,北京100021

出　　处：《中国药理学通报》2012年第5期695-700,共6页Chinese Pharmacological Bulletin

基　　金：国家"重大新药创制"科技重大专项"十一.五"课题资助(No 2008ZX09312-020);国家"重大新药创制"科技重大专项"十二.五"课题资助(No 2011ZX09101-001-13)

摘　　要：目的评价聚乙二醇重组人粒细胞集落刺激因子(PEG-rhG-CSF)注射液在化疗引起的中性粒细胞减少症中的药代动力学(PK)和药效学(PD)。方法入组24例肿瘤患者接受2个周期且剂量相同化疗方案,第1周期为对照周期,第2周期于化疗药物给药结束后48 h皮下注射不同剂量的PEG-rhG-CSF 1次,共设置60、100和150μg.kg-13个剂量组,每组受试患者8例,ELISA法检测受试者血清中PEG-rhG-CSF浓度,并计算PK参数,同时监测受试者CD34+、血常规、血生化指标变化。结果 PEG-rhG-CSF 3个剂量组主要药代参数如下:T12分别为(37.5±7)、(40.8±12)、(80.7±48)h;CL_F分别是(17±9)、(9±4)、(7±2)ml.h-1.g-1;AUC0-t分别是(5,593.6±5,435)、(14,651.3±12,183)、(23,002.5±6,655)mg.h.L-1。第2周期3个剂量组的中性粒细胞绝对值(ANC)最低点均值分别为1.9×109、2.3×109、4.2×109cells.L-1,均比第1周期有所提高。结论 PEG-rhG-CSF在体内呈现非线性药代动力学特征,其在体内维持药效时间长,1次注射即可达到较好疗效。Aim To evaluate the pharmacokinetics and pharmacodynamics of pegylated recombinant human granulocyte colony-stimulating factor（PEG-rhG-CSF） in the prophylaxis of chemotherapy-induced neutropenia.Methods 24 patients received two cycles of the same chemotherapy regimen.In cycle 1,patients were just treated with chemotherapy.In cycle 2,patients would receive a single subcutaneous injection of PEG-rhG-CSF（dose levels of 60,100 or 150 μg·kg-1,8 patients in each group） 48 hours after chemotherapy.PEG-rhG-CSF was detected in the serum by ELISA.The pharmacokinetic parameters were calculated by WinNonlin 5.2.1,meanwhile pharmacodynamic analysis was performed.Results The main pharmacokinetic parameters of PEG-rhG-CSF after three single dose injection were as follows：T1 2 was（37.5±7）,（40.8±12）,（80.7±48） h;CL_F was（17±9）,（9±4）,（7±2） ml·h-1·g-1;AUC0-t was（5,593.6±5,435）,（14,651.3±12,183）,（23,002.5±6,655） mg·h·L-1.The mean ANC nadirs were 1.9×109 cells·L-1,2.3×109 cells·L-1,4.2×109 cells·L-1 in cycle 2,which were higher than those in cycle 1.Conclusions The pharmacokinetics of PEG-rhG-CSF is a non-linear profile.It has a potential of once-per-cycle administration.

关 键 词：聚乙二醇化 重组人粒细胞集落刺激因子 药代动力学 药效学 酶联免疫分析法 临床Ⅰ期试验 

分 类 号：R329.12[医药卫生—人体解剖和组织胚胎学] R557.1[医药卫生—基础医学]