小児集中治療領域における統合的薬物動態評価と個別化投与設計

抄録

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.

Therefore, individualized dosing in pediatric intensive care should be comprehensively optimized by integrating the fundamental principles of pediatric pharmacotherapy and critical illness. Visualization of drug concentration profiles and prediction of treatment trajectories are practical strategies that facilitate multidisciplinary decision-making. Pharmacists play a central role in this process by integrating pharmacokinetic-pharmacodynamic knowledge with clinical information to anticipate changes in drug exposure and propose timely dose adjustments. Future advances in pharmacometrics (eg, population pharmacokinetic modeling, time-varying physiological modeling), and digital clinical decision support tools are expected to further enhance precision dosing and improve therapeutic outcomes in pediatric critical care.