Kearns Gregory L, Artman Michael
Arkansas Children's Hospital Research Institute and the Department of Pediatrics at the University of Arkansas for Medical Sciences.
Curr Pharm Des. 2015;21(39):5636-42. doi: 10.2174/1381612821666150901105337.
Over the past 30 years, much has been learned about the impact of development on drug disposition (i.e., pharmacokinetics). This is not true concerning drug action (i.e., pharmacodynamics). As a consequence, in clinical therapeutics and the drug development process, assumptions are often times made that a specific systemic drug exposure that is associated with desired drug action in adults will produce the same response in children. A review of the literature would suggest that this assumption may, in some cases, be an errant one. The relative paucity of information concerning developmental pharmacodynamics is associated with the challenge of assessing and quantitating drug response in vivo in infants and children. An approach to overcome these difficulties has been the evolution of biomarkers that are functional in nature in that they are capable of measuring drug response in both a time and age dependent fashion. The purpose of this review is to illustrate how functional biomarkers capable of assessing drug response/ effect in the developing child are developed and being evaluated for their clinical utility.
在过去30年里，人们对发育对药物处置（即药代动力学）的影响已有很多了解。但在药物作用（即药效动力学）方面却并非如此。因此，在临床治疗和药物研发过程中，常常会做出这样的假设：在成人中与期望的药物作用相关的特定全身药物暴露在儿童中会产生相同的反应。文献综述表明，在某些情况下，这一假设可能是错误的。关于发育药效动力学的信息相对匮乏，这与评估和定量婴儿及儿童体内药物反应的挑战有关。克服这些困难的一种方法是开发具有功能性质的生物标志物，因为它们能够以时间和年龄依赖的方式测量药物反应。本综述的目的是说明能够评估发育中儿童药物反应/效应的功能性生物标志物是如何开发的，以及正在如何评估其临床效用。
