Extrapolating the vancomycin population pharmacokinetic model for model-informed precision dosing in pediatric patients supported by external validation
Objective This study aimed to evaluate the predictive performance of the previously estimated vancomycin population pharmacokinetic(PopPK)model using data from pediatric populations with skin,soft tissue,and bone and joint infections,thus determining whether it can be extrapolated to other patient populations and guiding the individualized application of vancomycin in children.Methods The basic characteristics of pediatric patients,including age,gender,body weight,laboratory examination,and their blood concentrations of vancomycin from June 2021 to December 2022,were retrospectively extracted from the hospital information system.The pre-established population pharmacokinetic model of the pediatric patient group was reconstructed in the Phoenix software,and the individual predictive value of vancomycin for each patient was obtained through Bayes forecast,including the mean relative prediction error[MPE(％)],median relative prediction error[MDPE(％)],and root mean squared error(in percentage)(RMSE)for individual predictions,and external validation was carried out on the established pharmacokinetics model.Results A total of 399 vancomycin concentrations at steady state from 342 pediatric patients were included in the final external validation dataset.With the exception of newborns,based on observed and predicted values,the MPE(％)and MDPE(％)in infants,children and adolescents were within±20％,and the RMSE was within 30％.Based on the type of infection,the MPE(％)and MDPE(％)were within±20％and the RMSE was within 30％(31.1％in patients with respiratory infection)in pediatric patients with respiratory infection,central nervous system infection and other infections,excluding neonatal patients.Conclusion The previously established vancomycin PopPK model could be used in clinical practice in infants,children and adolescents to optimize vancomycin precise dosing,thereby guiding the individualized application of vancomycin in children.
Population pharmacokinetic modelExtrapolationVancomycinPediatric patientsModel-informed precision dosing
万方数据
维普
