卡培他滨在中国乳腺癌患者中的群体药代动力学研究  

Population pharmacokinetics of capecitabine in Chinese breast cancer patients

作　　者：徐国防 张思森[1,2] 刘平 梅家转[1,2] 刘玮玮[1,2] 刘亚欧[3] 齐琦 XU Guofang;ZHANG Sisen;LIU Ping;MEI Jiazhuan;LIU Weiwei;LIU Ya'ou;QI Qi(People's Hospital of Henan University of Chinese Medicine,Zhengzhou 450003,Henan,China;People's Hospital of Zhengzhou,Zhengzhou 450003,Henan,China;Department of Pharmacy,Peking University First Hospital,Beijing 100034,China;School of Medicine,Jinan University,Guangzhou 410632,Guangdong,China)

机构地区：[1]河南中医药大学人民医院,河南郑州450003 [2]郑州人民医院,河南郑州450003 [3]北京大学第一医院药剂科,北京100034 [4]基础医学院,暨南大学,广东广州510632

出　　处：《中国临床药理学与治疗学》2021年第5期552-559,共8页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金面上项目(81973341);广州市科技计划项目(202002030010)。

摘　　要：目的:评价卡培他滨在中国乳腺癌患者的群体药代动力学特征及可能的影响因素。方法:选取78例中国乳腺癌患者为研究对象,餐后单次口服卡培他滨片0.6 g(0.15 g/片,4片)后进行多点采集血样。以高效液相色谱-质谱联用法(HPLC-MS/MS)检测血浆中卡培他滨的血药浓度,以非线性混合效应软件及模型(NONMEM)对检测数据进行分析,建立卡培他滨群体药代动力学模型并获得其群体药代动力学参数。结果:最终建立的吸收及消除模型为一室模型,模型的清除率(CL/F)药代动力学公式为:CL/F=291×e^(ηCL)×(CCR÷93.1)^(0.47)。群体药代动力学参数如下:CL/F为291 L/h,表观分布容积(V/F)为556 L,吸收速率常数(K_(a))为1.05 h^(-1)。同时发现,肌酐清除率(CCR)对卡培他滨的清除有显著影响。结论:所得模型稳定,能较好地拟合卡培他滨在中国乳腺癌患者的群体药代动力学特征,可用于临床个体化给药方案的制订。AIM:To investigate the population pharmacokinetic characteristics of capecitabine and its possible influencing factors in Chinese patients of breast cancer.METHODS:78 cases of Chinese patients with breast cancer were chosen as the objects in this study.Following treatment with capecitabine(0.6 g,0.15 g/piece,4 pieces,orally),blood samples were collected and concentrations of capecitabine in plasma were analyzed by high performance liquid chromatography-mass spectrometry(HPLC-MS/MS)method.The nonlinear mixed-effects software(NONMEM)was used to analyze the data and the population pharmacokinetic model was constructed accordingly.RESULTS:The final established model of absorption and elimination is one-compartment model.The clearance(CL/F)in pharmacokinetic formula of the model is as follows:CL/F=291×e^(ηCL,i)×(CCR÷93.1)^(0.47).The typical pharmacokinetic parameters of the model are as follows:the clearance(CL/F)is 291 L/h;the apparent volume of distribution(V/F)is 556 L;the absorption rate constant(K_(a))is 1.05 h^(-1).In addition,the elimination of capecitabine can be notably influenced by creatinine clearance rate(CCR).CONCLUSION:The constructed model is stable,which fits features well of the population pharmacokinetics of capecitabine in Chinese patients with breast cancer.The modle can be utilized for the individualized administration plan in clinic.

关 键 词：卡培他滨 群体药代动力学 高效液相色谱-质谱联用法 乳腺癌 

分 类 号：R969[医药卫生—药理学]