Developmental Pharmacodynamics and Modeling in Pediatric Drug Development
Developmental Pharmacodynamics and Modeling in Pediatric Drug Development
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DOI：
10.1002/jcph.1482
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发表时间：
2019-09-01
影响因子：
2.9
通讯作者：
van den Anker, John
中科院分区：
文献类型：
--
作者：
Conklin, Laurie S.;Hoffman, Eric R.;van den Anker, John
儿科药物开发面临的挑战包括患者数量少、结果研究有限、伦理障碍和生物样本稀少。越来越多的儿童药物开发侧重于外推：利用关于成人疾病和药物反应的知识，为儿童亚群的药物和临床试验性能预测提供信息。药代动力学-药效学（PK-PD）模型和外推旨在减少建立疗效所需的患者数量和数据点。计划PK-PD和生物标志物研究应该在成人药物开发计划的早期开始。外推依赖于这样的假设，即潜在疾病和用于治疗该疾病的药物的作用机制在成人和儿科亚群中是相似的。显然，需要考虑PK和PD的发展变化，以提高PK-PD建模的质量，从而提高外推的成功率。这篇文章的重点是成人和儿科亚群之间PD差异的影响，这与外推法的使用高度相关。
Challenges in pediatric drug development include small patient numbers, limited outcomes research, ethical barriers, and sparse biosamples. Increasingly, pediatric drug development is focusing on extrapolation: leveraging knowledge about adult disease and drug responses to inform projections of drug and clinical trial performance in pediatric subpopulations. Pharmacokinetic-pharmacodynamic (PK-PD) modeling and extrapolation aim to reduce the numbers of patients and data points needed to establish efficacy. Planning for PK-PD and biomarker studies should begin early in the adult drug development program. Extrapolation relies on the assumption that both the underlying disease and the mechanism of action of the drug used to treat that disease are similar in adults and pediatric subpopulations. Clearly, developmental changes in PK and PD need to be considered to enhance the quality of PK-PD modeling and, therefore, increase the success of extrapolation. This article focuses on the influence of differences in PD between adults and pediatric subpopulations that are highly relevant for the use of extrapolation.