Population Pharmacokinetics of Vancomycin in Chinese Neonates / 中国药学杂志

ABSTRACT

OBJECTIVE: To investigate the population pharmacokinetics of vancomycin (VAN) in Chinese neonates by nonlinear mixes-effects modeling software (NONMEM). METHODS: One hundred and fifty-four VAN serum trough data from 91 neonatal patients were retrospectively collected from Suzhou Hospital Affiliated to Nanjing Medical University. A one-compartment model with first order elimination was used to describe structure pharmacokinetic model, and physiological maturity model was employed to screen covariates. The stability and prediction of the final model were evaluated by Bootstrap and normalized prediction distribution error (NPDE). The final model was applied to evaluate the percentage of AUC0-24 h/MIC ≥ 400 in neonatal patients by Monte Carlo Simulation, who were stratified according to gestational weeks, age and serum creatinine. RESULTS: The weight, postmenstrual age and serum creatinine were identified as the most significant covariate on clearance. Bootstrap and NPDE showed the satisfactory stability and prediction performance of the final model. Moreover, the final model indicated that 96% of neonates with low serum creatinine (15 μmol·L-1) were not getting AUC0-24 h/MIC≥400, according to the current guidelines. CONCLUSION: The population pharmacokinetic model of vancomycin in neonates is established successfully and could provide basis for the individualized therapy in neonatal patients.