Ince Ibrahim, de Wildt Saskia N, Tibboel Dick, Danhof Meindert, Knibbe Catherijne A J
Department of Pediatric Surgery, Erasmus MC Sophia Children's Hospital, Rotterdam, The Netherlands.
Drug Discov Today. 2009 Mar;14(5-6):316-20. doi: 10.1016/j.drudis.2008.11.004. Epub 2008 Dec 26.
Rational dosing guidelines for drugs in pediatrics are urgently needed. To develop these guidelines, we use population pharmacokinetic-pharmacodynamic (PK-PD) modeling and simulation by: (i) optimization of clinical trial designs based on preliminary data; (ii) development and internal validation of population PK-PD models using sparse data; (iii) external validation using independent data; and (iv) prospective clinical evaluation. Optimized dosing regimens for specific drugs may then serve as a basis to develop dosing guidelines for existing or newly developed drugs with similar disposition and/or effect. In addition to modeling of drug disposition (PK) pathways, we emphasize the need for modeling of effect (PD) pathways and the use of a multidisciplinary infrastructure for data-sharing.
迫切需要制定儿科药物的合理给药指南。为制定这些指南，我们采用群体药代动力学-药效学（PK-PD）建模与模拟，方法如下：（i）根据初步数据优化临床试验设计；（ii）使用稀疏数据开发群体PK-PD模型并进行内部验证；（iii）使用独立数据进行外部验证；（iv）进行前瞻性临床评估。然后，特定药物的优化给药方案可作为为具有相似处置和/或效应的现有或新开发药物制定给药指南的基础。除了对药物处置（PK）途径进行建模外，我们还强调需要对效应（PD）途径进行建模，并使用多学科基础设施进行数据共享。
