Pharmacokinetics and Childhood Obesity: Pathophysiological Basis and Challenges in Choosing the Ideal Body Size Descriptor

TL;DR

This paper reviews how obesity in children affects drug metabolism and highlights the need for better dosing strategies tailored to obese pediatric patients.

Contribution

The paper systematically evaluates pathophysiological changes in obese children and their impact on drug pharmacokinetics, emphasizing the need for new dosing strategies.

Findings

Obese children show altered pharmacokinetics due to changes in body composition and organ function.

Hydrophilic drugs have increased distribution volume, while lipophilic drugs show variable distribution.

Drug clearance may be modified due to altered liver and kidney function in obese children.

Abstract

Despite the progressive increase in obesity and associated chronic diseases in children, there is limited evidence on the optimal dosage of most medications for obese children and adolescents. This review analyzes the influence of pathophysiological changes on pharmacokinetics and pharmacodynamics and evaluates the body size descriptors used in clinical practice. Patients with obesity present significant pathophysiological alterations, such as a substantial increase in fat/lean mass ratio, increased blood flow and cardiac output, and changes in plasma protein binding, which may affect the volume of distribution of drugs and the adjustment of the loading dose. In these patients, the distribution volume of hydrophilic drugs appears to slightly increase, while it varies widely—depending on the drug and other factors such as affinity for other tissues—for lipophilic drugs. On the other hand, a reduction in tissue perfusion, alterations to liver enzyme activity, and an increase in liver and kidney mass and blood flow have been reported, indicating a possible modification in drug clearance and necessitating adjustments to maintenance regimens. Furthermore, while there are multiple size descriptors, it is difficult to establish a single dosing strategy for the obese population, given the lack of studies confirming the extent of changes in pharmacokinetic processes, which will also depend on the properties of each drug, such as liposolubility and elimination pathways. New strategies need to be developed to characterize pharmacokinetic and pharmacodynamic changes in the obese pediatric population in order to optimize dosing regimens and improve the safety and efficacy of treatments.

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