中国临床药理学与治疗学2017，Vol.22Issue(7)：767-774,804,9.
比较美罗培南传统延长和优化延长输注在脓毒症大鼠不同组织中的药代动力学/药效动力学
Pharmacokinetics and pharmacodynamics of meropene administered by traditional prolonged infusion or optimized prolonged infusion in different tissues of septic rats
摘要
Abstract
AIM:To study the pharmacokinetics of meropenem infused through different methods in varied parts of septic rats by microdialysis and to evaluate the pharmacodynamics of the two different infusion methods using of Monte Carlo simulation.METHODS:Twelve male Sprague Dawley rats were randomly divided into two groups (traditional prolonged infusion vs.the optimized prolonged infusion,n =6) for the pharmacokinetics study.Microdialysis probes were inserted into the jugular vein,hind leg muscle,subcutaneous adipose tissue and lung.Pharmacokinetic parameters were calculated by non-compartmental analysis.Monte Carlo simulations(10 000 rats) were performed to calculate 40％ fT＞MIC and the probability of target attainment (PTA) at different MICs,then to compare the effect of two infusion models.RESULTS:The tissue distribution factors (AU C tissue(0 to 6 h)/AUC pl (0 to 6 h) ratio) of the two groups were both less than 1 for lung,muscle and subcutaneous adipose tissue relative to plasma;the Tmaxs in plasma,lung,muscle and subcutaneous adipose tissue had statistically difference between the optimized prolonged infusion group and the traditional prolonged infusion method group;at different MICs,using the optimized prolonged infusion method,the PTA values of the 40％ fT ＞MIC for the free meropenem in different tissues were higher than using the traditional prolonged infusion method.CONCLUSION:Using total plasma concentrations can overestimate the antibacterial activity of the drug and therefore its clinical efficacy.According to the pharmacokinetic of meropenem in the target infected tissues is more reasonable than plasma to guide the meropenem dosing regimen.Optimized prolonged infusion method is likely more reasonable than traditional prolonged infusion method.关键词
脓毒症/药代动力学/药效动力学/美罗培南/蒙特卡洛模拟Key words
sepsis/pharmacokinetics/pharmacodynamics/meropenem/Monte Carlo simulation分类
医药卫生引用本文复制引用
吴永磊,王丹,张睢扬,王英,孙芹..比较美罗培南传统延长和优化延长输注在脓毒症大鼠不同组织中的药代动力学/药效动力学[J].中国临床药理学与治疗学,2017,22(7):767-774,804,9.基金项目
国家自然科学基金青年项目(81301662) （81301662）
北京市科技新星计划(Z161100004916165) （Z161100004916165）
