Development of Vancomycin Population Pharmacokinetic Models for Pediatric Patients Using a Real-World Web Application...

The Japanese Society of Chemotherapy developed practical area under the concentration-time curve (AUC)-guided therapeutic drug monitoring (PAT), a freely available web-based application widely used in Japan to support AUC-guided dosing of vancomycin. Its broad adoption has generated a substantial real-world pharmacokinetic database. Although PAT includes a preliminary pediatric model based on data from American children aged 3 months or older, that model requires further optimization. This study aimed to develop a population pharmacokinetic (popPK) model specifically for Japanese pediatric patients and to compare its performance with existing models.

We utilized a real-world database collected through PAT between December 2022 and October 2024, comprising 1673 pediatric patients aged 3 months or older. Population pharmacokinetic analysis was performed using nonlinear mixed-effects modeling, with comparisons made against 5 existing models.

The developed model demonstrated strong a priori predictive performance for empirical vancomycin dosing, with a mean prediction error of 0.2 μg/mL and a mean absolute prediction error of 5.6 μg/mL. These results showed no apparent bias. Graphical diagnostics confirmed optimal a priori prediction in the developed model. A posteriori predictive performance-used for Bayesian posterior dosing-was similarly favorable across all models. Notably, 2-point sampling produced significantly different clearance estimates compared with 1-point sampling in 21 of 116 patients (18.1%).

For Japanese pediatric patients aged 3 months or older, the developed popPK model is suitable for both empirical and Bayesian-guided vancomycin dosing. Two-point sampling improves the accuracy of clearance estimation and is recommended when feasible.