摘要
目的研究羟基喜树碱在肿瘤患者的群体药动学(PPK)特征,为临床调整肿瘤患者的个体用药提供新途径。方法60例肿瘤患者静脉滴注羟基喜树碱后,采集不同时间的静脉血样260个点,HPLC测定羟基喜树碱的血药浓度。以非线性混合效应模型(NONMEM)程序法分析羟基喜树碱群体药代动力学参数。结果羟基喜树碱二室模型最终的群体药动学参数群体标准值CL1,V1,CL2,V2分别为(18.3±4.71)L.h-1,(12.6±2.15)L,(18.3±2.32)L.h-1,(26.8±4.81)L。男性的中央室清除率是女性的1.512倍,群体模型有较好的拟合优度。结论NONMEM法对二室模型群体参数估算的血药浓度值与实测值有良好的相关性,性别对中央室清除率参数影响较大。本试验获得的羟基喜树碱群体参数可以为羟基喜树碱在肿瘤病人的临床个体化用药提供支持。
OBJECTIVE To investigate population pharmacokinetics （PPK） of hydroxycamptothecine （HCPT） after constant intravenous infusion in cancer patients. METHODS Sixty cancer patients were involved. All 260 plasma concentrations of HCPT were determined by HPLC. The influences of age, gender, body weight and biochemical indicator on parameters were evaluated by using NONMEM software. PPK models of HCPT were finally established. RESULTS The pharmacokinetics of HCPT was described by a two-compartment pharmacokinetic model. Final two-compartment pharrnacokinetic model parameters of HCPT were as follows： CL1（ 18.3±4.71 ） L.h^-1, Vj （12.6±2.15） L, CL2 （18.3±2.32） L.hl and V2 （26.8±4.81） L. The clearance in male cancer patients was 1.512 times as that in females. The predicted concentrations of HCPT showed a good correlation with measured concentration. CONCLUSION Gender significantly impacts on clearance in HCPT. Dose regimens of HCPT were finally established for clinical different cancer patients based on the PPK parameters. Population pharmacokinetic parameters of HCPT is helpful for the individual regimens in clinics.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2009年第15期1168-1172,共5页
Chinese Pharmaceutical Journal
基金
江苏省医学科技发展基金临床药学科研项目(P200415)
关键词
肿瘤患者
羟基喜树碱
群体药动学
非线性混合效应模型
高效液相色谱法
cancer patient
hydroxycamptothecine
population pharmacokinetics
nonlinear mixed effect model
highperformance liquid chromatogram
