米氏消除药物血管外给药的方案设计

Dosage Regimen Design of Drugs Obeying First Brder Absorption and Michaelis-Menten Clearance Kinetics

目的获得(一级并行)米氏消除药物血管外给药的方案设计。方法根据四阶Runge-Kutta算法,采用Excel软件编写基于药动学参数的给药方案设计程序。结果输入药动学参数Vm,Km,Vd/F,Ke,Ka和给药间隔τs后,Excel规划求解获得最大维持剂量(dmax)和最低维持剂量(dmin);输入选定的维持量(d)及初始浓度后,电子表格显示某周期(或稳态)任一次给药后相隔时间为0.005 h的血药浓度和AUC值,获得有效血药浓度时间(tec)和达坪分数[f(n)],Excel单变量求解获得负荷剂量。结论该方法编程简单,使用方便,既能为临床用药提供安全有效的剂量,又能对某一用药方案作出评价。

OBJECTIVE To establish a method for the dosage regimen design of drugs obeying first order absorption and Michaelis- Menten clearance kinetics. METHODS By four stages Runge-Kutta algorithm and Microsoft Excel, the program of dosage regimen design was written on the basis of pharmacokinetic parameters. RESULTS After inputting the pharmacokinetic parameters（ Vm, Km, Vd/F, ke and ka ） and dosing interval（rs）, maximum maintenance dose（dmax） and minimum maintenance dose（dmin） was obtained. After inputting maintenance dose selected between dmax and dmin, plasma concentrations at 0.005 h interval after the administration were displayed. The fractional number of reaching plateau（f） and effective concentration time（tec） were obtained. The loading dose was obtained by single variable solution. CONCLUSION This simple program provids safe and effective dosage for clinical drug-use.