Samant Tanay S, Mangal Naveen, Lukacova Viera, Schmidt Stephan
Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Lake Nona (Orlando), FL, USA.
Simulations Plus, Inc., Lancaster, CA, USA.
J Clin Pharmacol. 2015 Nov;55(11):1207-17. doi: 10.1002/jcph.555. Epub 2015 Jul 15.
The establishment of drug dosing in children is often hindered by the lack of actual pediatric efficacy and safety data. To overcome this limitation, scaling approaches are frequently employed to leverage adult clinical information for informing pediatric dosing. The objective of this review is to provide a comprehensive overview of the different scaling approaches used in pediatric pharmacotherapy as well as their proper implementation in drug development and clinical use. We will start out with a brief overview of the current regulatory requirements in pediatric drug development, followed by a review of the most commonly employed scaling approaches in increasing order of complexity ranging from simple body weight-based dosing to physiologically-based pharmacokinetic (PBPK) modeling approaches. Each of the presented approaches has advantages and limitations, which will be highlighted throughout the course of the review by the use of clinically-relevant examples. The choice of the approach employed consequently depends on the clinical question at hand and the availability of sufficient clinical data. The main effort while establishing and qualifying these scaling approaches should be directed towards the development of safe and effective dosing regimens in children rather than identifying the best model, ie models should be fit for purpose.
儿童药物剂量的确定常常因缺乏实际的儿科疗效和安全性数据而受到阻碍。为克服这一限制，常采用比例换算方法，利用成人临床信息来确定儿科用药剂量。本综述的目的是全面概述儿科药物治疗中使用的不同比例换算方法，以及它们在药物研发和临床应用中的正确实施。我们将首先简要概述儿科药物研发的当前监管要求，随后按复杂度递增顺序回顾最常用的比例换算方法，从基于简单体重的给药到基于生理的药代动力学（PBPK）建模方法。所介绍的每种方法都有其优点和局限性，在综述过程中将通过使用临床相关实例予以强调。因此，所采用方法的选择取决于手头的临床问题以及足够临床数据的可获得性。建立和验证这些比例换算方法时的主要努力应指向制定儿童安全有效的给药方案，而非确定最佳模型，即模型应适合其用途。
