Hitting the Target: Model-Informed Precision Dosing of Tobramycin in Pediatric Patients with Cystic Fibrosis

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Abstract
Background: Tobramycin is a key therapy for pulmonary exacerbations in children and adolescents with cystic fibrosis (CF), yet its variable pharmacokinetics (PK) combined with narrow therapeutic index necessitates therapeutic drug monitoring (TDM) during clinical care to optimize exposure while minimizing toxicity. Model-informed precision dosing (MIPD) is a potentially powerful tool to support dose individualization in clinical care that leverages population PK models and Bayesian forecasting. Herein, we evaluated the performance of an MIPD initiative at our hospital for once-daily tobramycin in pediatric patients with CF. Methods: Tobramycin practices at a single CF center before (2016–2018) and after (2019–2025) implementation of an MIPD initiative in CF patients < 21 years were evaluated. TDM during the pre-MIPD period used traditional log-linear AUC calculations, while the post-MIPD period used a commercial MIPD software platform integrated within the electronic health record. Outcomes included attainment of the target 24 h area-under-the-curve (AUC24 80–120 mg·h/L), number of TDM samples and dose adjustments during the first 7 days of treatment, and rates of acute kidney injury (AKI). Results: A total of 114 treatment courses were analyzed (77 pre-MIPD, 37 post-MIPD). Post-MIPD target attainment was 75.7% at TDM1, 89.2% at TDM2, and 100% at TDM3, significantly higher than pre-MIPD at corresponding cycles. The post-MIPD period required fewer TDM samples (4.2 vs. 7.1; p < 0.001) and dose adjustments (0.7 vs. 1.8; p < 0.001) in the first 7 days. AKI incidence remained low and comparable between periods. Conclusions: Implementation of an MIPD initiative for tobramycin in pediatric patients with CF led to the early attainment of therapeutic AUC24 targets while reducing TDM burden and dose adjustments.

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