Investigation Of Population Pharmacokinetics Of Vancomycin In Infant Patients

Aim1 To establish the population pharmacokinetics(PPK) model of vancomycin(VCM) in infant patients.2 To analyze the clinical application mode by the PPK model of VCM.Methods1 Cases who received the VCM therapy in our hospitalized infant patients. The information including sex, age, body weight, liver function, renal function and drugs combination was recorded. Blood samples were collected when sparse trough concentrations at steady state in patients given conventional VCM dosing regimen by intravenous infusion. Serum concentration of VCM was analyzed by enzyme multiple immunoassay technique(EMIT).2 Evaluate the fixed effects and the random effects on the clearance rate of VCM by nonlinear mixed effects mode and establish the full amount of regression models of VCM by stepwise regression, and then build the final model via the backward regression.3 Graphic method is used to evaluate the superiority of model fitting, the stability and internal validity of the model is explored by Bootstrap; then appraise the forecast ability of the model by normalized predictive distribution error(NPDE) and external validation.4 Combining with PPK model of VCM, edit Bayesian feedback code, to simulate the steady-state concentration under different administration regimens of VCM via Bayesian feedback method.Results The PPK final regression model of VCM was established based on 155 trough concentrations of the 52 patients; as follow:Weight:WT;Blood urea nitrogen:BUN;T:intravenous time;t:monitoring time The final model has been confirmed by Plots Analysis, and the goodness of fit index is fairly good.and most of the forecasted concentration weighted residual difference actually between ±2. The steady rate verified by Bootstrap was 95.8 %, and relative deviation was less than 2.00 %, the estimated parameters of final model values within the 95 % confidence interval. NPDE examination showed the homogeneity of variance.Conclusions1 WT and BUN are the major covariate of PPK of VCM.2 TDM combinations with Bayesian feedback can provide information for rational clinical use of drug.