重组葡激酶群体药动学研究  

Population pharmacokinetics of recombinant staphylokinase

作　　者：张弨[1] 翟所迪[1] 杨丽[1] 郭静萱[2] 李海燕[2] 

机构地区：[1]北京大学第三医院药剂科 [2]北京大学第三医院心内科,北京100083

出　　处：《中国新药杂志》2004年第4期341-344,共4页Chinese Journal of New Drugs

基　　金：国家高技术研究发展计划(863计划)(2003AA2Z3413)

摘　　要：目的:应用非线性混合效应模型(NONMEM)法研究重组葡激酶(r-SAK)的群体药动学。方法:建立双抗体酶联免疫吸附法(ELISA)测定r-SAK的血浆药物浓度,应用NONMEM法进行模型优化,确定r-SAK的药动学模型和统计学模型,估算群体药动学参数和个体间、个体内变异,并进行统计分析。结果:建立了r-SAK的特异性浓度测定方法。r-SAK符合二房室一级消除模型,体重(WET)和肌酐对k21有显著性影响,方程为k21=θ(3)×WETθ(5),最终估算结果:k=0.19h-1,k12=1.93h-1,k21=1.87×10-4×WET1.84h-1,V=13.2L。计算所有参数的SE(Standard error)和95％CI(Confidence interval)评价参数估算方法的优劣。结论:应用NONMEM法估算出的群体药动学参数结果可全面给出药物的药动学参数和变异,为r-SAK的安全性和有效性研究提供了丰富的依据。Objective:To study the population pharmacokinetics of recombinant staphylokinase (r-SAK) by means of nonlinear mixed effect model (NONMEM). Methods: Plasma drug concentration was determined by dual antibody ELISA method; the population pharmacokinetics model was optimized by NONMEM; and population pharmacokinetic parameters and variability were calculated. Results: The pharmacokinetics of r-SAK confirm to 2-compartment first order elimination model and the body weight and creatinine had significant effect on k21(k21 =θ(3)×WETθ(5) ) and the final parameters were:k=0.19h-1,k12=1.93h-1,k21= 1.87×10-4×WET1.84h-1, V=13.2L.The standard error and 95% confidence interval of all parameters were calculated. Conclusion: All the pharmacokinetic parameters and variability can be estimated by NONMEM and provided sufficient proof for the safety and efficacy of r-SAK.

关 键 词：群体药动学 重组葡激酶 非线性混合效应模型法 

分 类 号：R969.1[医药卫生—药理学] R972.7[医药卫生—药学]