摘要
目的建立多西他赛在肿瘤患者中的群体药动学(PPK)模型,考察固定效应因素对多西他赛清除率的影响。方法以接受多西他赛静脉滴注的肿瘤患者为研究对象,回顾性分析80例患者服药后的210个多西他赛的稳态血药浓度及相应的实验室指标检测数据,多西他赛的血药浓度采用高效液相色谱法测定,应用非线性混合效应模型(NONMEM)软件进行PPK数据分析,Bootstrap重复抽样用于模型的内部验证。结果建立最终模型方程为:CL'=θ1×(BSA/1.58)θ2×(ALB/3.6)θ3×HEP,患者体表面积、白蛋白和肝功能对多西他赛的清除率影响显著。结论利用NONMEM软件建立针对肿瘤患者的多西他赛PPK模型,并结合患者体表面积、白蛋白和肝功能可估算其清除率,为临床个体化用药方案的优化提供参考。
Objective To establish the population pharmacokinetic （PPK） model of docetaxel in patients, and to provide theory base for personalized drug use. Methods A total of 210 sparse serum concentration data of docetaxel were collected from 80 oncosis patients following intravenous drip infusion. The plasma concentration of docetaxel was determined by HPLC method. PPK data analysis was performed using nonlinear mixed effect model （NONMEM） software. The bootstrap assay was applied for internal validation. Results The final PPK model for docetaxel was listed below： CL＇=0~ x （BSA/1.58）~2~ （ALB/3.6）HEP. There was significant influence on clearance such as body surface area, albumin and hepatic dysfunction. Conclusion The PPK model of docetaxel is successfully conducted with NONMEM, which can estimate clearance through body surface area, albumin and hepatic dysfunction to optimize individual drug use.
出处
《世界临床药物》
CAS
2012年第12期734-738,共5页
World Clinical Drug
关键词
多西他赛
群体药动学
非线性混合效应模型
docetaxel
population pharmacokinetics
nonlinear mixed effect model
