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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 study the population pharmacokinetics (PPK) characteristics of hydroxycamptothecin in cancer patients and to provide a new way to adjust the individual medication in patients with cancer. Methods Sixty patients with tumor were intravenously injected with hydroxycamptothecin, and 260 venous blood samples were collected at different times. The plasma concentrations of hydroxycamptothecin were determined by HPLC. The pharmacokinetic parameters of hydroxycamptothecin were analyzed by non-linear mixed-effects model (NONMEM) program. Results The standard values of CL1, V1, CL2 and V2 in the two groups were (18.3 ± 4.71) Lh-1, (12.6 ± 2.15) L and (18.3 ± 2.32) Lh- 1, (26.8 ± 4.81) L. Men’s central ventricular clearance rate is 1.512 times that of women, the population model has better fitness. Conclusion The NONMEM method has a good correlation with the measured values of plasma concentration estimated by the two-compartment model population parameters, and gender has a great influence on the clearance parameters of the central ventricle. The population of hydroxycamptothecin groups obtained in this study may provide support for the clinical individualization of hydroxycamptothecin in cancer patients.