The PK/PD Research Of Different Target Site That Shows Meropenem’s Effect On Sepsis Rats Those Used Routine Dosage And Traditional Infusion Methods

Objective: using microdialysis technology and Monte Carlo simulation toresearchthe PK/PDofdifferenttargetsitethat shows Meropenem’s effect on sepsis rats those used routine dosage and traditional infusion methods.Methods: Firstly, we will check the microdialysis linear probe and plasma probe in vivo and vitro;ThenusingCLPmethodpreparationofdifferentlevels(mild、moderate、severe)sepsisintherats,throughbloodsamplinginthe different timepointsdeterminingthedeliverytime; Finally using the well-checked probe to study the drug concentration-time curve of different target site that used Meropenem in routine dosage and traditional infusion methods and using the WinNonlin software to calculate the pharmacokinetic parameter of Meropenem; using the above pharmacokinetic parameter and Monte Carlo simulation to conclude the pharmacodynamical parameter such as MIC value %T>MIC,Cmax>MIC、PTA of Meropenem’s effect on sepsis rats those used routine dosage and traditional infusion methods.Results: 1 、 For the purposes of this experiment using WinNonlin5.2 software simulation of sepsis rats and normal rats of the same target parts of a pharmacokinetic parameters of statistical analysis, Sepsis in the rat lung, blood plasma, and skeletal muscle of Vd ismore than normal rats of Vd, sepsis in the rat plasma and subcutaneous of CL is greater than normal rats of CL,the difference was statistically significant, other sepsis rats and normal rats the same target parts of a pharmacokinetic parameters between the difference is not significant. For sepsis rats and normal rats pharmacokinetic parameters between different target areas of statistical analysis, respectively, in addition to the sepsis in the rat lung CL outweigh the CL of plasma and lung of CL is greater than that of skeletal muscle tissue CL difference was statistically significant, the rest of the pharmacokinetic parameters of sepsis rats and normal in the rat pharmacokinetic parameters of the above technology in various parts of the distribution difference had no statistical significance.2、For the purposes of this experiment using WinNonlin5.2 software simulation of sepsis rats and normal rats between the same target site(lung, skin, skeletal muscle) of fTfor the statistical analysis, all differences had no statistical significance, prompt sepsis did not change the organization of the target tissue penetration. For sepsis rats and normal rats of different target area(lung, skin, skeletal muscle) of fT statistical analysis respectively, normal rats skeletal muscle fT is greater than the subcutaneous tissue fT, sepsisrats skeletal muscle fT is greater than the lung fT and skeletal muscle fT is greater than the subcutaneous tissue fT, the difference was statistically significant.3、Under the circumstance of routine dosage and traditional infusion methods,normal rats four target area in particular MIC value(0.5, 1, 2, 4)(% T > MIC) greater than or equal to 40 probability of target, in addition to the MIC = 0.5 mg/L in plasma and skeletal muscle tissue can achieve 40% probability of target, the rest are all below 40%;Forsepsis rats four target areas in particular MIC value(0.5, 1, 2, 4)(% T > MIC) under 40 or higher probability of target is below 40%. In normal rats and sepsis rats Cmax/MIC ratio are very high, And(Cmax/MIC) greater than or equal to 4 can achieve 100% probability.Conclusion:1、Microdialysis technology can be used to study the PK/PD of sepsis rats’ different target site.2、Sepsis has changed the pharmacokinetic parameters of different target parts of rats(Vd、CL)and the tissue penetration, the difference was statistically significant. We can’t simply use the research of normal rats to represent that of sepsis rats.3、Meropenem’s used in routine dosage and traditional infusion methods,sepsis in rats of different target areas for specific MIC value amounted to less than optimal PTA.We should optimize the dosage regimen is increasing to the dose, drug delivery times or prolong delivery time in order to achieve effective clinical effect.