术中植入缓释氟尿嘧啶在直肠癌患者中的群体药动学研究  

Population Pharmacokinetics of Sustained-release 5-Fluorouracil for Implantation in Colorectal Cancer Patients

作　　者：翟丹丹[1] 吕雄文[1] 张震[2] 邓子煜 

机构地区：[1]安徽医科大学药学院,合肥230032 [2]安徽医科大学第一附属医院 [3]合肥亿帆药业有限公司

出　　处：《中国药师》2013年第2期163-166,共4页China Pharmacist

基　　金：安徽省高校自然科学重点研究项目(编号:KJ2009A033);安徽省卫生厅青年基金项目(编号:09B129)

摘　　要：目的:建立并考察直肠癌患者术中植入氟尿嘧啶的群体药动学(PPK)模型,为直肠癌患者的临床用药提供个体化指导。方法:通过完整的药动学(PK)采样法收集20名直肠癌患者的血药浓度120个。一室模型为基础,通过使用非线性效应模型拟合法(NONMEM)建立群体药动学模型,考察固定效应(身高、体质量、年龄、性别、肝肾功能、联合用药等)对氟尿嘧啶PK参数的影响。结果:氟尿嘧啶植入剂PPK参数为:Ke(0.005 44±0.002 89)h^(-1),Ka(0.748±0.602)h^(-1),V/F(1.06±0.343)L·kg^(-1),Ke(0.005 7±0.541)h^(-1),CL/F(262±0.194)L·kg^(-1)。模拟1 000个受试者的数据,结果显示血药浓度的90%可信区间基本涵盖实测值,证实了模拟结果的可靠性。结论:本研究成功建立氟尿嘧啶植入剂的群体药动学模型,可以估算个体药动学参数预测血药浓度,满足优化个体化给药的需要。Objective： To observe the population pharmacokinetie model of sustained-release 5-fluorouracil for implantation in colorectal cancer patients in order to offer the individual therapy. Method： Totally 120 human plasma samples from 20 colorectal canc- er patients were collected using complete pharmacokinetic sampling method. First-order compartment model as the base, the population pharmacokinetie model was established by NONMEM. The fixed effects, such as height, weight, sex, hepatorenal function and drug combination etc on the pharmacokinetie parameters of 5-fluorouracil were observed. Result： The population pharmacokinetic parameters of sustained-release 5-fluorouraeil for implantation in coloreetal cancer patients were as follows ： Kr was 0.005 44 ＋ 0.002 89 h - l, Ka was 0.748 ~0.602 h-1, V/F was 1.06 ~0.343 L ~ kg-1, Ke was 0.005 7 ~0.541 h-1 and CL/F was 262 ~0. 194 L ~ kg-1. The 90% confidence interval covered the measured values using the simulated blood concentration in 1 000 patients, suggesting the reliabil- ity of the results. Conclusion： The population pharmacokinetic model of sustained-release 5-fluorouracil for implantation is successfully found, which can estimate individual pharmacokinetie parameters, forecast human plasma and meet the requirements of individual drug therapy in colorectal cancer patients.

关 键 词：氟尿嘧啶 植入剂 群体药动学 非线性效应拟合法 

分 类 号：R969.1[医药卫生—药理学]