NONMEM法分析静滴异丙酚在中国人体的群体药代动力学

Evaluation of population pharmacokinetics of propofol with NONMEM in Chinese patients

目的 考察中国人静脉匀速滴注异丙酚的群体药代动力学。方法 51例腰麻-硬膜外联合麻醉病人匀速输注异丙酚直至暴发脑电抑制,以HPLC法测定异丙酚血浆浓度,用NONMEM程序分析中国人异丙酚群体药代动力学。结果 异丙酚药代动力学符合三室线性开放模型,群体参数CL(L.min-1)、Vc(L)、Q2(L.min-1)、V2(L)、Q3(L.min-1)和V3(L)的标准值分别为1.10,7.63,1.54,15.0,0.76和175;体重对CL的校正为体重除以60的0.70次方,CL和Q2年龄≥60的病人较年龄<60的分别低18.1%和32.1%;年龄对V2和Q3的校正分别为年龄除以50的-0.66次方和-0.71次方。结论 NONMEM法对以三室模型群体参数估算的血药浓度值与实测值有良好相关性,体重、年龄对参数影响较大。

Objective To investigate the population pharmacokinetics (PPK) ofpropofol (PPF) after constant intravenous infusion in Chinese patients. MethodsFifty one selective surgical patients with combined spinal and epidural anesthesiawere analyzed. The constant intravenous infusion of PPF lasted until burstsuppression of electroencephalogram. Plasma concentrations of PPF weredetermined by HPLC. The PPK modeling was performed with NONMEM program.Results The linear three compartment open model had a goodness of fit for PPFpharmacokinetics. The standard values of CL(L.min-1),Vc(L),Q2(L.min-1),V2(L),Q3(L.min-1) and V3(L) were 1.10, 7.63, 1.54, 15.0, 0.76 and 175, respectively. Therevision of body weight to CL was described by a power function of body weight/60 with 0.70. If age ≥60, the CL and Q2 of patients were respectively lower of 18.1%and 32.1% than the others. The revision of age to V2 and Q3 were respectivelydescribed by a power function of age/50 with -0.66 and -0.71. Conclusion Therewas a good relationship between the measured concentrations and the predictedvalues calculated from the PPK model and parameters. The PPK parameters weremainly influenced by age and body weight of patients.