Establishment of a Vancomycin Population Pharmacokinetic Model for Pediatric Patients Based on the Non-Linear Mixed-Effects Model

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BACKGROUND AND OBJECTIVES: Vancomycin (VCM) pharmacokinetic parameters vary widely between individuals. Existing models developed domestically and internationally may not apply universally because of differences in patient populations and testing methodologies. Therefore, the present study aimed to address the clinical challenge of optimizing individualized VCM dosing in pediatric patients at the study institution by developing a VCM population pharmacokinetic model and identifying key factors influencing VCM clearance, thereby providing a reference for safe and effective clinical dosing strategies. METHODS: Data regarding 124 effective VCM concentrations and 100 pediatric patients who received intravenous VCM were retrospectively collected. We used a non-linear mixed-effects model with forward inclusion and backward elimination to create the final VCM population pharmacokinetic model. The model was internally validated using bootstrapping, goodness of fit, and visual predictive check. The Monte Carlo method was used to simulate the range of trough concentrations in pediatric patients with renal insufficiency and normal function under different dosing regimens. RESULTS: A one-compartment model adequately described the pharmacokinetic behavior of VCM in vivo. The typical values of clearance and volume of distribution were 8.22 L/h and 113 L, respectively. Renal function and body weight were the most important factors affecting the clearance of VCM. The model was validated as stable and reliable. CONCLUSIONS: The VCM population pharmacokinetic model established during this study can assist physicians with the development and optimization of dosing regimens for pediatric patients.

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