Integrated Pharmacokinetic Assessment and Individualized Dosing in Pediatric Critical Care

Abstract

Optimizing pharmacotherapy in pediatric intensive care requires an integrated understanding of developmental physiology and critical illness-related pathophysiology. Drug exposure in children cannot be interpreted as a simple scaled version of adult pharmacokinetics. Critically ill pediatric patients frequently experience rapid and dynamic changes in organ function, fluid balance, and treatment modalities, all of which can substantially modify drug disposition. Systemic inflammation, capillary leakage, and hypoalbuminemia often increase the volume of hydrophilic drug distribution in the intensive care setting, potentially leading to subtherapeutic exposure during the early treatment phase. Subsequently, augmented renal clearance or acute kidney injury may occur, resulting in underexposure or drug accumulation, respectively. Extracorporeal therapies further complicate dosing decisions by introducing additional clearance pathways and drug sequestration.