Population Pharmacokinetics of Amikacin in Non-Neonatal Pediatric Patients: A Scoping Review.

BACKGROUND

Amikacin remains an important agent in managing severe Gram-negative infections in children. However, its clinical use is limited by a narrow therapeutic index and pronounced pharmacokinetic (PK) variability. Population pharmacokinetic (PopPK) modeling offers a framework for individualized dosing, yet evidence in non-neonatal pediatric populations remains fragmented.

METHODS

A scoping review was conducted across PubMed, Scopus, and Web of Science (last updated July 2025) to identify PopPK studies evaluating intravenous amikacin in children aged 1 month to 18 years. Eligible studies applied nonlinear mixed effects modeling and reported structural models, PK parameters, and covariate analyses. Methodological quality was assessed using a 38-item checklist adapted from established guidelines.

RESULTS

Of 783 records screened, 8 studies met the inclusion criteria. Most were retrospective, with sparse PK sampling from routine therapeutic drug monitoring (TDM) data. Body weight was the most consistently identified predictor, while renal function, age, and disease state were retained in selected models. Burn, cystic fibrosis, and oncology populations demonstrated consistently higher clearance and/or volume of distribution, often requiring higher doses for pharmacodynamic target attainment. None of the included studies performed external validation, limiting generalizability.

CONCLUSIONS

Amikacin PK in children is highly variable and disease-specific. Conventional weight-based dosing is frequently insufficient. Integration of model-informed precision dosing (MIPD) with TDM is essential to optimize amikacin therapy in pediatric practice, particularly in high-risk subpopulations.