Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Tokyo, 194-8543, Japan; Clinical Pharmacology Department, Chugai Pharmaceutical Co., Ltd., Chuo-ku, Tokyo, Japan.
Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Tokyo, 194-8543, Japan.
Drug Metab Pharmacokinet. 2021 Aug;39:100394. doi: 10.1016/j.dmpk.2021.100394. Epub 2021 Mar 29.
The accidental ingestion of drugs is a common concern, especially in the case of young children. A physiologically based pharmacokinetic (PBPK) model that implements the age-dependent size growth and ontogeny of organ functions can be used to predict the concentration-time profiles of drugs in the pediatric population. In this study, the feasibility of using a PBPK model for predicting the amount of drug accidentally swallowed by a child was assessed based on a case study in an infant. Alprazolam was the drug involved in the current case. The developed PBPK model of alprazolam was first evaluated using pharmacokinetic data obtained in healthy adult male volunteers. Then, it was adapted for application to virtual Japanese pediatric subjects having the same demographic information as the infant of interest. The pharmacokinetic data observed in the infant fell within the range of the 5th and 95th percentiles of the pharmacokinetic simulations after administration of 0.4 mg alprazolam (equivalent to one tablet) in the panel of virtual infants. PBPK simulations could provide estimates of the amount accidentally ingested by a child and also give mechanistic insights into the observed drug concentrations. The current study demonstrates the potential clinical utility of PBPK modeling.
药物的意外摄入是一个常见的关注点，特别是对于婴幼儿。一种基于生理学的药代动力学（PBPK）模型，可实现器官功能的年龄依赖性大小增长和个体发育，可用于预测儿科人群中药物的浓度-时间曲线。在本研究中，基于对婴儿病例的研究，评估了使用 PBPK 模型预测儿童意外吞咽药物量的可行性。涉及的药物为阿普唑仑。首先，使用在健康成年男性志愿者中获得的药代动力学数据评估了阿普唑仑的开发 PBPK 模型。然后，对其进行了改编，以应用于具有与感兴趣婴儿相同人口统计学信息的虚拟日本儿科受试者。在给予 0.4mg 阿普唑仑（相当于一片）后，在虚拟婴儿组中观察到的婴儿药代动力学数据落在药代动力学模拟的第 5 和第 95 个百分位数范围内。PBPK 模拟可以估计儿童意外摄入的量，并为观察到的药物浓度提供机制见解。本研究证明了 PBPK 建模的潜在临床应用。
