ArticleFrontiers in pharmacology2025
Physiologically-based pharmacokinetic modeling and simulation for initial dose optimization of levetiracetam in pediatrics.
Article in Frontiers in pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Optimizing levetiracetam (LEV) dosing in children is challenging due to high pharmacokinetic variability, which often necessitates empirical dose titration. This study aimed to develop and verify a physiologically-based pharmacokinetic (PBPK) modeling and simulation to guide and optimize initial LEV dose selection in pediatric patients. Methods: A whole-body PBPK model for LEV was developed and verified in adults, then scaled and verified in a pediatric population (0.5-12 years). This model was used to simulate various dosing regimens. Subsequently, a multivariate linear regression (MLR) analysis correlated key covariates (dose, regimen, body weight, and glomerular filtration rate) with simulated steady-state peak (C Results: The MLR model successfully explained over 90% of the variance (R Conclusion: The combined PBPK-MLR approach provides a robust, data-driven framework to support rational first-dose prescriptions of LEV in children. This tool has the potential to accelerate therapeutic effects while enhancing treatment individualization. Prospective clinical validation is required to confirm the model predictive performance for drug exposure and, consequently, its impact on therapeutic efficacy.
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