Daousani Chrysa, Karalis Vangelis D
Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens, Greece.
Drug Res (Stuttg). 2017 Jul;67(7):377-384. doi: 10.1055/s-0043-109788. Epub 2017 May 18.
In the past, dosage regimens authorized for adults were extrapolated to children relying mainly on empirical dosage adjustments. However, children are not small adults, but a distinct and heterogeneous group in terms of physiology, disease occurrence, pharmacokinetics, pharmacodynamics and also psychological, cognitive, and behavioral aspects. Even though it would be helpful to know the physiological changes and the special drug treatment needs in children, this task could not be performed due to ethical reasons. Important issues to consider for the development of paediatric drug products refer to the administration of the accurate dose, the use of the appropriate excipients, and acceptability. The latter is crucial and taste-screening methods (like electronic tongues) have been developed. A new era in paediatric medicines started with the entry into force of paediatric regulations. In the early '80s, the FDA started the set-up of a regulatory framework by authorizing issues like the Paediatric Rule, the Best Pharmaceuticals for Children Act, the Paediatric Research Equity Act, and the Food and Drug Administration Safety and Innovation Act. Similar efforts have been made in the EU, mainly through the entry into force of the Paediatric Regulation and the establishment of the Paediatric Committee, the Paediatric Investigation Plan, the Paediatric Use Marketing Authorization, and the European Paediatric Research Network. Other efforts to bridge the gap, between knowledge in adults and the children's special requirements, include the extrapolation concept of safety/efficacy aspects, the application of modeling/simulation approaches in paediatric drug development, and the development of a paediatric Biopharmaceutics Classification Scheme.
过去，批准用于成人的给药方案主要依靠经验性剂量调整来推算用于儿童。然而，儿童并非缩小版的成人，而是在生理、疾病发生、药代动力学、药效学以及心理、认知和行为方面都截然不同且具有异质性的群体。尽管了解儿童的生理变化和特殊药物治疗需求会有所帮助，但出于伦理原因，这项工作无法开展。开发儿科药品时需要考虑的重要问题包括准确剂量的给药、合适辅料的使用以及可接受性。后者至关重要，并且已经开发出了味觉筛选方法（如电子舌）。随着儿科法规的生效，儿科药物的新时代拉开了帷幕。20世纪80年代初，美国食品药品监督管理局（FDA）开始建立监管框架，批准了诸如《儿科规则》《儿童最佳药品法案》《儿科研究公平法案》以及《食品药品管理局安全与创新法案》等相关事宜。欧盟也做出了类似努力，主要是通过《儿科法规》的生效以及成立儿科委员会、儿科研究计划、儿科用途上市许可和欧洲儿科研究网络。为弥合成人知识与儿童特殊需求之间的差距所做的其他努力，包括安全性/有效性方面的外推概念、儿科药物开发中建模/模拟方法的应用以及儿科生物药剂学分类系统的开发。
