(一级并行)米氏消除药物静脉滴注给药的方案设计

The Dosage Regimen Design of Multiple Intravenous Instillations of Drugs Obeying Parallel First Order Michaelis-Menten Elimination Kinetics

目的建立米氏消除药物多次静脉滴注给药方案设计方法。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、ke和给药间隔sτ后,Excel规划求解获得最大维持剂量(dm ax)和最低维持剂量(dm in);输入选定的维持量(d)及初始浓度后,电子表格显示一周期(或稳态)任一次给药后小的相隔时间(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。结论该方法设计简单,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 set up a method for the design of dosage regimen of drugs administered by multiple intravenous instillations obeying the parallel first order Michaelis-Menten elimination kinetics. Methods According to the fourstage Runge-Kutta algorithm, we used Microsoft Excel to write a design program for dosage regime based on pharmacokinetic parameters. Results Maximum maintenance dose （dmax） and minimum maintenance dose（ dmin ） were obtained by program solution after inputting the pharmacokinetic parameters （ Vm, Km, Vd, ke ） and dosing interval （ τs ）. Following the input of selected maintenance dose （d） and initial concentration, the Excel displayed plasma concentration of the drug and AUC value at mini-interval （H） after any single administration within one cycle as well as fractional number of reaching plateau （ F^[n] ） and the time of effective blood concentration of the drug （ Tec ）. The loading dose was obtained by single variable solution. Conclusion The design of the method was simple and capable not only of providing safe and effective dosages for the clinical administration of drugs but also offering assessment of the dosage regimen of a definite drug.