间接药动-药效模型参数的计算程序

Program design of indirect pharmacokinetic and pharmacodynamic model

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.