Compare The Parameters Of PK/PD Of Different Infusion Model In Optimized Two-step Infusion Therapy Of Meropenem

Objective:In clinical lower respiratory tract infection patients, to determine plasma concentrations ofmeropenem of the dosing regimens of optimized two-step infusion therapy with0.5h/250mg+2.5h/750mg in the experimental group and with0.5h/500mg+2.5h/500mg in thecontrol group,respectively, and thus to obtaine meropenem’s pharmacokinetic parametersin a specific patients, and to calculate Cmax/MIC,%T>MIC and PTAs in these infusionmodels based on different MICs, then to compare the efficacy of two infusion method.Method:20clinical mild, severe bacterial lower respiratory tract infection were collected throughthe inclusion and exclusion standard,they were completely randomized into experimentalgroup and control group with10cases in each group, to collect the patient’s generaldemographic data, the experimental group was infused with0.5h/250mg+2.5h/750mginfusion model,and the control group was infused with0.5h/500mg+2.5h/500mginfusion model; when in transfusion,to extract5ml blood with the time of0h,0.25h,0.5h,1h,1.5h,2h,3h,3.5h,4h,5h,6h,8h,respectively, in different intravenousinfusion vein, immediately to centrifugate10minutes with3000rpm and extract from thesupernatant and store at–25℃refrigerator. the plasma concentration of the patients weredetermined by Using high performance liquid chromatographic internal standard method,the pharmacokinetics of meropenem, such as plasma clearance （CL）, the apparent volumeof distribution （Vd）, the elimination half-life (t_1/2), peak concentration （Cmax）, time topeak （Tmax）, the area under the curve （AUC） and other pharmacokinetic parameters,wereobtained by Winnonlin5.2software with the measured plasma concentration-time profiles; using Crystal Ball software to perform Monte Carlo simulation （MCS） in order to calculateCmax/MIC,%T>MIC and PTAs according to the PK/PD model, then to compare theeffect of two infusion models.Results:The experimental group and the control group patients were consistent with mild、severe bacterial lower respiratory tract infection, the sex ratio, age, weight, and creatinine values and APACHEⅡ score between the two groups had no significant difference, the mean values of plasma concentration of the experimental group and thecontrol group patients determined by using high performance liquid chromatographyinternal standard method when the time of0h,0.25h,0.5h,1h,1.5h,2h,3h,3.5h,4h,5h,6h,8h were0.21,2.44,5.20,9.60,12.99,12.05,9.20,8.54,7.75,6.40,5.60,4.09and1.38,7.10,10.21,13.31,14.48,15.31,12.44,9.60,7.36,4.53,3.13,1.33,respectively; Vd of the experimental group was35.51±3.33, t_1/2was1.59±0.26, CL was14.80±1.11, Tmax was1.48±0.12, Cmax was11.86±0.54, AUC was64.40±4.62, Vd of the control group was29.13±4.21, t_1/2was1.32±0.34, CL was14.41±1.76, Tmax was1.95±0.11, Cmax was15.25±0.93, AUC was64.56±7.38; in MIC were1,2,4μg/ml, Cmax/MIC of the experimental group performed with Monte Carlo simulation were6.40±0.55,3.20±0.27,1.60±0.14,respectively;%T>MIC were118.94±9.71,97.13±7.20,74.28±4.77,respectively; PTAs were all100%; Cmax/MIC of the control group were15.46±1.97,7.71±0.98,3.87±0.49,respectively;%T> MIC were105.70±13.92,87.29±10.60,68.58±7.29,respectively; PTAs were all100%.Conclusion:Cmax/MIC was smaller with infusion model of0.5h/250mg+2.5h/750mg compared withinfusion model of0.5h/500mg+2.5h/500mg in optimized two-step infusion therapy ofmeropenem, but%T>MIC of the experimental group was great than the control group, thePTAs of two groups were all100%, the results revealed that the experimental group mightbe superior to the control group, the infusion model of0.5h/250mg+2.5h/750mg can beused in clinical to treat infection.