非线性混合效应模型法估算肾移植患者环孢素A的相对清除率

Estimation of relative clearance of cyclosporin A with nonlinear mixed effect model in kidney transplant patients

目的用非线性混合效应模型(NONMEM)法定量考察年龄、性别、体重、合并用药、肝功能、合并症和服药持续时间对清除率的影响。方法收集中山大学附属第一医院由1999～2001年临床221例肾移植患者323人次肾移植后服用环孢素A(CsA)3d以上谷值浓度,应用SAS程序估算其药动学参数(参考NONMEM程序一步法)。结果按口服吸收一室开放模型的群体药动学参数清除率CL、表观分布容积Vd分别等于13.46L·h-1,228.2L,浓度观察值与模型预测值的残差变异σE(%)等于0.0065。其个体间变异σCL(%)为5.94。CL(L·h-1)的最终回归方程为CL=13.46-0.063A+0.082W。其中A为患者年龄;W为患者体重(kg)。结论年龄越大,CL越小;体重越大,CL越大。

OBJECTIVE To investigate the infIuence of age,sex,body weight,rapamune,diltiazem,nifedipine,hepatic function,incorporate symptom and lasting time of taking CsA on CL with nonlinear mixed effect model. METHODS 323 blood samples of CsA on steady state trough level were collected from 221 kidney transplant patients from 1999 to 2001, who have continuously administrated CsA for over 3 d. To evaluate the parameters through program SAS（referring to the NONMEM program）. RESULTS One-compartment open model with firstorder absorption and elimination was used to analyze the data. The main parameters of population pharmacokinetic were as follows：CL（L/h） was 13.46,Va（L） was 228.2. σE（%） was 0. 006 5,σCL（%） was 5.94. The final regression equation of CL（L/h） was： CL= 13.46-0.063 A ＋ 0. 082 W,in which A was the age,W was the total body weight（kg）. CONCLUSION The clearance of CsA decrease while the age is older; the clearance of increase while the body weight is higher.