Population Pharmacokinetics Analysis Of Vancomycin In Elderly Patients

Objective:To establish the PPK model of VCM in elderly patients.Method:Collect the elderly patients(age>65) receiving vancomycin therapy and record the detailed informations of age, gender, body weight, hepatorenal function and co-administration. Blood samples were collected from each patient at least once to twice when his or her blood vancomycin concentration was considerd to have reached steady state, and were determined the vancomycin serum concentrations by enzyme multiplied immunoassay technique (EMIT). Nonlinear mixed effects modeling program was used to establish one-compartment model in geriatric, and evaluate the fixed effects and the random effects on the clearance rate of VCM. Then established the full amount of regression models of VCM by stepwise regression, and built the final model via the backward regression. Finally, evaluated the stability and the predictive ability of final model by plots, bootstrap method and normalized predictive distribution error(NPDE).Result:Based on182trough concentrations of the100patients, established the PPK final model of vancomycin, as follow:CL=4.23×(CLCr/76.83)0.774×e0.345V=71.4(L). Creatinine clearance (CLcr) was the most important factor affect CL. Plots revealed the final model was proforming a goodness fit, and most of the predicted comcentration values weights residuals between+2. The steady rate verified by Bootstrap was100%, and relative deviation was less than2.00%, estimated value of final model was in the95%CI by Bootstrap method. NPDE showed homogeneity of variance and a normal distribution.Conclusion:The PPK model of VCM in geriatric established in this study was authenticated to have satisfied stability and predictive efficacy, and is suitable to provide basis for individualized dosage regimens.