Standing Joseph F, Tsolia Maria, Lutsar Irja
Infectious Diseases and Microbiology Unit, University College London, Institute of Child Health, London, WC1N 1EH, UK.
Infect Disord Drug Targets. 2013 Feb;13(1):6-14. doi: 10.2174/18715265112129990003.
Pharmacokinetic-pharmacodynamic (PKPD) studies have the potential to yield useful information on whether and how a drug works, and what dose to use. This approach is often best suited to situations where dose-response relationships need to be elucidated and where randomisation is not feasible. Children make up around one third of cases during influenza outbreaks, and are more susceptible to certain complications such as otitis media. Despite this, high-quality randomised controlled trials (RCT) of antiviral therapies such as oseltamivir have not been performed, leaving open the question of whether and at what dose to use. This review therefore focusses on the available PKPD data in children. Oseltamivir has complex PK which requires modelling to properly understand the relationship between dose and concentration with time, and there is a lack of clarity on appropriate pharmacodynamic endpoints. Following a general overview of oseltamivir PKPD, this review seeks to summarise the available paediatric PKPD data, identify gaps in our knowledge and priorities for future research.
药代动力学-药效学（PKPD）研究有潜力提供关于药物是否起作用、如何起作用以及使用何种剂量的有用信息。这种方法通常最适用于需要阐明剂量-反应关系且随机化不可行的情况。在流感暴发期间，儿童病例约占三分之一，并且更容易患某些并发症，如中耳炎。尽管如此，尚未开展诸如对奥司他韦等抗病毒疗法进行的高质量随机对照试验（RCT），这使得使用与否以及使用何种剂量的问题悬而未决。因此，本综述重点关注儿童中现有的PKPD数据。奥司他韦具有复杂的药代动力学，需要进行建模以正确理解剂量与浓度随时间的关系，并且在合适的药效学终点方面缺乏明确性。在对奥司他韦的PKPD进行总体概述之后，本综述旨在总结现有的儿科PKPD数据，找出我们知识上的差距以及未来研究的重点。
