肝移植患者术后口服他克莫司群体药动学研究  

Population pharmacokinetics of tacrolimus in liver transplant patients

作　　者：王浩[1] 孙丽莹[2] 饶伟[2] 孙晓叶[2] 王楠[2] 章袁[2] 朱立勤[2] 

机构地区：[1]天津医科大学第一中心临床学院,天津300192 [2]天津市第一中心医院,天津300192

出　　处：《中国新药杂志》2013年第4期447-451,共5页Chinese Journal of New Drugs

基　　金：天津市卫生局科研课题(2011KY09)

摘　　要：目的:考察肝移植患者术后口服他克莫司的群体药动学模型,为临床个体化用药提供参考。方法:回顾性收集天津市第一中心医院18例肝移植患者术后口服他克莫司12 h全血药浓度监测数据145个。运用非线性混合效应模型(nonlinear mixed effect model,NONMEM)建立他克莫司群体药动学模型,并考察了年龄、性别、移植术后天数、血清肌酐等固定效应对药动学参数的影响,得到最终模型方程,最后利用Bayesian反馈得到的个体药动学参数值进行个体化给药方案设计。结果:本次研究建立起了口服他克莫司一级吸收和消除的二房室群体药动学模型,并通过NONMEM模拟程序为1例患者进行了个体化给药设计。结论:NONMEM法建立的模型能较好地估算他克莫司的个体及群体药动学参数,为临床合理使用他克莫司提供参考依据。Objective ： To investigate a population pharmacokinetics （PPK） model of oral tacrolimus in liver transplant patients and to provide reference for individualized medication in clinical practice. Methods： Totally 145 blood concentration data of tacrolimus were retrospectively collected from 18 full liver transplant patients in Tianjin First Center Hospital. A NONMEM PPK model was set up. The fixed effects including age, gender, post- operative day and serum creatinine on parameters of PPK were estimated, and the final model was built. The individual pharmacokinetic parameters were obtained using the Bayesian feedback, and individual dosage was designed. Results： A two-compartment model with first-order absorption and elimination was built, and an individual dosage design for a patient by NONMEM simulation procedure was completed. Conclusion： The obtained model by NONMEM can estimate the population and individual pharmacokinetics of tacrolimus and offer reference for the individualized dosage of tacrolimus in clinical practice.

关 键 词：他克莫司 群体药动学 肝移植 非线性混合效应模型 个体化给药 

分 类 号：R978.1[医药卫生—药品]