Physiologically Based Pharmacokinetic Modeling of Vancomycin and its Comparison with Population Pharmacokinetic Model in Neonates

Abstract

Vancomycin has a narrow therapeutic window and a high inter-individual pharmacokinetic variability, especially in neonates with fast maturational and pathophysiological changes, that needs individualized dosing. Physiologically based pharmacokinetic (PBPK) model and population pharmacokinetic (PopPK) model are both useful tools in model-informed precision dosing, while the former is under research in application of vancomycin in neonates. This study aimed to develop a PBPK model of vancomycin in adult and pediatric population, and compared it with published PopPK model (priori or Bayesian method) in predicting vancomycin concentration in 230 neonatal patients (postmenstrual age, PMA, 25-45 weeks). The developed PBPK model showed a good fit between predictions and observations. PBPK model and PopPK model are complementary in different clinical scenarios of vancomycin application. The physiological-change description of PBPK model showed a superior advantage in initial dosing optimization. As for subsequent dose optimization, PopPK Bayesian forecasting performed better than the PBPK estimation in neonates. However, initial precision dosing tools for early neonates (with PMA < 36 weeks) still need further exploitation.