Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
J Clin Pharmacol. 2024 Jun;64(6):697-703. doi: 10.1002/jcph.2405. Epub 2024 Jan 31.
Food effect (FE) studies characterize food-drug interactions that may alter the efficacy or safety of a drug, but these studies are not conducted in pediatric patients. Pediatric patients have substantial physiologic, anatomic, and dietary differences from adults, which may result in differences in their FE considerations. Therefore, the objective of this study was to identify oral drug products approved for use in pediatric patients aged <6 years with an FE observed in adults. Additional objectives were to summarize the therapeutic areas, pharmacokinetic effects, and labeling instructions that resulted from these studies. Publicly available data were searched for products studied in pediatric patients and approved for use by the United States Food and Drug Administration (FDA) from 2012 to 2022. Of the 102 oral drug products approved for use in patients aged <6 years, 43 recommended the consideration of food intake in the drug labeling. These included drug products recommended to be taken with food (n = 21, 49%) or without food (n = 14, 33%). Each of the 14 drug products recommended to be taken without food are approved for use in pediatric patients aged <2 years. The products approved for use in pediatric patients aged <2 years comprised the highest proportion with area under the plasma concentration-time curve extrapolated to infinity (AUC, n = 35, 75%) and maximum serum concentration (C, n = 45, 80%) affected by food. Close monitoring is warranted during the postapproval period for products identified as having a significant FE in adults and that are approved for use in pediatric patients aged <6 years. Promising tools for predicting pediatric FE may include physiologically based pharmacokinetic absorption modeling.
食物效应（FE）研究描述了可能改变药物疗效或安全性的药物-食物相互作用，但这些研究并未在儿科患者中进行。儿科患者与成人在生理、解剖和饮食方面存在显著差异，这可能导致他们在 FE 方面存在差异。因此，本研究的目的是确定在成人中观察到食物效应的情况下，批准用于 <6 岁儿科患者的口服药物产品。其他目标是总结这些研究产生的治疗领域、药代动力学效应和标签说明。公开数据中搜索了在儿科患者中进行研究并获得美国食品和药物管理局（FDA）批准用于 <6 岁患者使用的产品。在批准用于 <6 岁患者的 102 种口服药物产品中，43 种建议在药物标签中考虑食物摄入。这包括建议与食物一起服用的药物产品（n = 21，49%）或不与食物一起服用的药物产品（n = 14，33%）。建议不与食物一起服用的 14 种药物产品均获准用于 <2 岁的儿科患者。获准用于 <2 岁儿科患者的产品包含受食物影响的血浆浓度-时间曲线下面积外推至无穷大（AUC，n = 35，75%）和最大血清浓度（C，n = 45，80%）比例最高。对于在成人中具有显著食物效应并获准用于 <6 岁儿科患者的产品，在批准后期间需要进行密切监测。用于预测儿科食物效应的有前途的工具可能包括基于生理学的药代动力学吸收建模。
