Study On Population Pharmacokinetic And Individualized Administration Of Vancomycin

Objective1. To establish the PPK model of VCM in Chinese population.2. To discuss the clinical application mode of the PPK model of vancomycin.Method1. The study involved the cases of hospitalized patients receiving vancomycin therapy,record age, sex, body weight, hepatorenal function and co-administration et al.Conventional dosing regimen of intravenous vancomycin in patients, collecting sparsetrough concentrations which have reached steady state blood samples.2. To determine the vancomycin serum concentrations via enzyme multipliedimmunoassay technique (EMIT).3. Evaluate the fixed effects and the random effects on the clearance rate of VCM bynonlinear mixed effects mode and establish the full amount of regression models ofVCM by stepwise regression, and then build the final model via the backwardregression.4. Evaluate the model fitting by plots; Evaluate stability and internal validity of themodel by Bootstrap; Evaluate the predictive ability of the model by normalizedpredictive distribution error(NPDE) and external validation.5. Associated with the established PPK model of VCM, write Bayesian forecastingprogram, to simulate the steady-state trough concentration under differentadministration regimens of vancomycin via Bayesian forecasting method.Result1. Base on179trough concentrations of the100patients, establish the PPK finalregression model of vancomycin, as follow: Creatinine clearance (CLcr) is the most important factor affect CL.2. Plots revealed the model was stable and effective with more accuracy than thesimple model. The steady rate verified by Bootstrap was100%, relative deviation wasless than2.00%, estimated value of final model was in the2.5%-97.5%CI byBootstrap method. NPDE showed homogeneity of variance and a normal distribution.In the simple model, MPE=-4.90, MAE=6.67and RMSE=9.83; in the final modelMPE=-2.99, MAE=4.56and RMSE=6.56; the accuracy and precision were improvedsignificantly in final model.3. The clinical application mode of vancomycin has been established and employed inclinical practice of individual drug administration.Conclusion1. The PKK model of VCM is established in the present study is of great stability andpredictive ability, which could provide individualized dosage regimens.2. The clinical application mode of PPK model of vancomycin established in thepresent study could promote rational use of medication.