Population pharmacokinetics of vancomycin in non-extremely preterm neonates based on real-world studies: influence of daily fluid input and diuretics

Abstract

ABSTRACT This study aimed to develop a population pharmacokinetics (PPK) model for vancomycin in non-extremely preterm neonates hospitalized in the neonatal intensive care unit (NICU), identify key factors affecting vancomycin pharmacokinetics in this patient population, and formulate an initial dosing protocol. A cohort of 126 neonates admitted to the NICU and treated with vancomycin at Northwest Women’s and Children’s Hospital from January 2019 to December 2023 were included in the study, resulting in the collection of 276 vancomycin concentration values. A PPK model for vancomycin was constructed using a nonlinear mixed-effects approach. The predictive power and stability of the final model were assessed through visual predictive checks, normalized prediction distribution errors, and bootstrapping. Serum creatinine (Scr) level, body weight, daily fluid input, and diuretic usage were identified as significant covariates affecting vancomycin clearance. Utilizing Monte Carlo simulations with the established model, initial recommended dosing regimens for neonates with varying Scr levels, daily fluid input, and diuretic use were estimated. The pharmacokinetic-pharmacodynamic model developed for vancomycin in non-extremely preterm neonates in the neonatal intensive care unit in this study may provide a theoretical reference for research on individualized medication.IMPORTANCEA population pharmacokinetic model for vancomycin in neonatal intensive care unit neonates was developed. Daily fluid input and the use of diuretic agents were identified as new significant covariates influencing drug clearance. Based on these covariates, a dosing regimen was developed that provides clinicians with individualized dosing recommendations.

Keywords

• neonates
• vancomycin
• pharmacokinetic model
• therapeutic drug monitoring
• model-informed precision dosing