Development and application of neonatal physiology-based pharmacokinetic models of amikacin and fosfomycin to assess pharmacodynamic target attainment.

ABSTRACT: Antimicrobial resistance increasingly complicates neonatal sepsis in a global context. Fosfomycin and amikacin are two agents being tested in an ongoing multicenter neonatal sepsis trial. Although neonatal pharmacokinetics (PKs) have been described for these drugs, the physiological variability within neonatal populations makes population PKs in this group uncertain. Physiologically-based pharmacokinetic (PBPK) models were developed in Simcyp for fosfomycin and amikacin sequentially for adult, pediatric, and neonatal populations, with visual and quantitative validation compared to observed data at each stage. Simulations were performed using the final validated neonatal models to determine drug exposures for each drug across a demographic range, with probability of target attainment (PTA)

SUBMITTER: Darlow CA 

PROVIDER: S-EPMC10941605 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature