间接药动-药效模型参数的计算程序  

Program design of indirect pharmacokinetic and pharmacodynamic model

作　　者：陈渊成[1] 曹彦光[1] 郝琨[1] 柳晓泉[1] 王广基[1] 

机构地区：[1]中国药科大学药物代谢与动力学研究中心,南京210009

出　　处：《中国药科大学学报》2007年第1期55-59,共5页Journal of China Pharmaceutical University

基　　金：国家高技术研究发展计划("八六三"计划)资助项目(No.2003AA2Z347A);江苏省药物代谢动力学重点实验室资助项目(No.BM2001201)~~

摘　　要：目的:根据Dayneka等人提出的间接药动学-药效模型,设计一种计算机程序,用于估算间接药动学-药效模型的参数。方法:联合应用遗传算法和规划求解同时拟合给药后血药浓度-时间和效应-时间的数据,估算相应的药动学和药效学参数。结果:以口服一房室模型为例,对华法林的间接药动学和药效学结合模型的曲线进行拟合,算得PK参数tmax(3.40±1.52)h,cmax(56.39±6.85)μg/mL,t1/2(20.14±5.66)h;PD参数Kin(0.1009±0.0193)h-1,Kout(0.0938±0.0174)h-1,IC50(3.732±1.336)mg/L。结论:该程序可用于间接药动学-药效模型参数的求算,并同时描述药物的药动学和药效学行为特征。Aim： A programme was designed to obtain the parameters of indirect pharmacokinetic-phannacedynamic model proposed by Dayneka. Methods： Using both genetic algorithm and planning solution, the parameters of the model can be estimated through simultaneous fitting of concentration-time data and response-time data. Results： Taking one compartment model following oral administration as example, the pharmacokinetic parameters value from curve fitting of the model of warfarin were： tmax（3.40 ± 1.52）h, cmax（56.39 ± 6.85） μg/mL, t1/2（20.14 ± 5.66）h; the pharmacodynamic parameters value were Kin（0. 100 9 ± 0.019 3）h^- 1, Kout（0.093 8 ± 0.017 4）h^ - 1, IC50（3.732 ± 1.336 ） mg/L. Conclusion： The application of the programme in obtaining parameters value of indirect pharmacokinetic-phannacedynamic model and characterization of the phannacokinetic/phannacedynamic behaviour of a drug had practical value in use.

关 键 词：间接药动学-药效学模型 华法林 遗传算法 规划求解 

分 类 号：R96[医药卫生—药理学]