Evaluation of the Effects of Childhood Obesity on Drug Dosing
Anil Maharaj, PhD
BACKGROUND: Obesity-related physiologic changes result in important alterations in drug exposure and dosing. However, there are only a few investigations to inform dosing in children with obesity, resulting in an urgent, unmet public health need.
GAP: The proposed research will determine the most important clinical and drug-specific factors that influence drug pharmacokinetics (PK) in obese children and provide an effective dosing strategy for this population.
HYPOTHESIS: Fat-free mass and primary drug elimination route (e.g., hepatic vs. renal) will be identified as influential covariates modulating drug PK between obese and non-obese children.
METHODS: The study will evaluate plasma concentrations for 8 different drugs collected from obese and non-obese children who received drugs of interest per standard of care. A multi-drug linear-mixed effect model will be developed to determine the most important clinical and drug-specific factors that influence PK in children with obesity.
IMPACT: This proposal will determine, for the first time in children, the most informative clinical and drug-specific factors to guide drug dosing in obese children. The results of this work will provide pediatric practitioners with an effective strategy for dosing their obese patients, lowering the risk of toxicity and therapeutic failures in this population.