单室模型的最佳给药方案

Optimal dosing strategy for one-compartment model

药物剂量和给药间隔时间的确定是临床给药方案设计中的关键问题。给药剂量过小无药效;剂量过大容易引起药物中毒。药物动力学用房室模拟人体,把给药后药物能迅速在周身各部位达到动态平衡的整个机体视为一个房室。针对单室模型的最佳给药方案问题,首先利用常微分方程建立"静注+静滴"的联合给药数学模型,在上次滴注与下次滴注初始剂量相同且等于首剂量的条件下确定重复给药体内药量的表达式;然后构建用积分来表示药量在人体内积蓄程度的目标函数,采用最优化方法,确定给药时间间隔、首次剂量、滴注时间和每天滴注次数等参数,进而得到使体内的毒素积蓄最小、安全有效的最佳给药方案。最后仿真结果表明,该方法可行有效。

Determinations of dose and dosing interval are key issues in clinical dosing strategy design.Too few doses can not make drugs effective;excessive doses can easily cause drug toxicity.In pharmacokinetic,compartment is used to simulate human body,and the whole organism,among which drugs can quickly reach dynamic balance after once dosing,is seen as a compartment.For the issue of the optimal dosing strategy under one-compartment model,firstly,differential equations are used to establish a unite dosing mathematical model of＂intravenous injection＋intravenous drip＂,and for repeated dosing,the expression of dose in vivo is determined under the condition that the initial dose in vivo of each drip is equal;then integral is employed to build an objection function which represents the accumulation degree of dose in vivo,and optimization method is utilized to determine parameters such as dosing interval,first dose,drip time,the number of drip each day,then the optimal dosing strategy,which is safe,efficient and accumulates the least toxins in vivo,is obtained;finally,simulation results show the feasibility and effectiveness of this method.