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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 a population pharmacokinetics (PPK) model of docetaxel in cancer patients and investigate the effect of fixed effect factors on the rate of docetaxel clearance. Methods Tumor patients receiving intravenous docetaxel were enrolled in this study. The steady-state plasma concentrations of 210 docetaxel in 80 patients and corresponding laboratory data were retrospectively analyzed. Docetaxel Race plasma concentrations were measured by high performance liquid chromatography (HPLC). Nonlinear mixed-effects model (NONMEM) software was used for PPK data analysis. Bootstrap was used for internal validation of the model. Results The final model equation was established as follows: CL ’= θ1 × (BSA / 1.58) θ2 × (ALB / 3.6) θ3 × HEP. The body surface area, albumin and liver function significantly affected the clearance rate of docetaxel. Conclusion The docetaxel PPK model for cancer patients was established by using NONMEM software. Combined with the body surface area, albumin and liver function, the clearance rate of docetaxel can be estimated, which can provide a reference for the optimization of clinical individualized drug regimen.