用SAS迭代及蒙特卡罗模拟优化美罗培南的使用

Use of SAS iteration and Monte Carlo simulation to optimize use of Meropenem

目的:筛选出针对临床上不同MIC值细菌时美罗培南的最优的药物剂量和点滴方式,同时比较传统、延长及优化两步点滴法的药效学。方法:首先用SAS迭代的方法筛选出在不同的MIC值时美罗培南两步点滴法时最优的药物剂量和点滴方式,然后使用蒙特卡罗模拟计算传统、延长及优化两步点滴法时的%T>MIC的值和达标概率。结果:在SAS迭代时,MIC为1、2、4μg/mL及CL和Vd取均数时,分别按500mg,0.25h/100mg+2.75h/400 mg;500mg,0.25h/250mg+2.75h/250mg和1000mg;0.25h/400mg+2.75h/600mg的优化两步点滴法的模型最优。在不同的MIC时,蒙特卡罗模拟均显示出在延长点滴和优化两步点滴法比传统点滴法有更高的%T>MIC和达标概率,优化两步点滴法比延长点滴法的达峰时间更短。结论:SAS迭代可以用来筛选出最优的药物剂量和点滴方式,同时蒙特卡罗模拟可以用来比较不同点滴方式的药效学。结果显示优化两步点滴法是更好的治疗临床严重感染的方法。

ABSTRACT AIM： To choose optimized dosages and regimens of Meropenem based on different MICs of clinical organisms, meanwhile to evalu- ate pharmacodynamics of traditional（TIT）, pro- longed （PIT） and optimized two-step infusion therapy （OTIT） of Meropenem. METHODS： Firstly, use of SAS iteration to choose optimized dosages and regimens of Meropenem based on different MICs of clinical organisms in the condi-tion of two-step infusion therapy; secondly, use of Monte Carlo Simulation to calculate the % T 〉MIC and the probability of target attainments （PTAs） of TIT, PIT and OTIT, respectively. RESULTS： Based on the and means of CL and Vd OTIT with 500 mg, 0. 400 rag; 500 rag, 0.25 mg and 1000 rag, 0.25 MICs of 1,2,4 μg/mL , the dosing regimens of 25 h/100 mg＋2.75 h/ h/250 mg＋2.75 h/250 h/400 mg＋ 2.75 h/600mg provided the highest %T〉MIC with SAS it- eration, respectively. Monte Carlo Simulation revealed that PIT and OTIT obtained higher % T 〉MIC and PTAs compared with TIT at differ- ent MICs, Meanwhile OTIT obtained shorter the time to maximum concentration（t ） compared with PIT. CONCLUSION： SAS iteration may be performed to choose the best optimized dosagesand regimens of antibiotics. Monte Carlo simula- tion may be performed to compare pharmacody- namic parameters of different dosing regimens. These results suggested that OTIT was better therapy against clinically serious infections.