Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indiana University, Indianapolis, Indiana, USA.
Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indiana University, Indianapolis, Indiana, USA.
Pharmacotherapy. 2023 May;43(5):391-402. doi: 10.1002/phar.2765. Epub 2023 Jan 25.
Maternal and pediatric populations have historically been considered "therapeutic orphans" due to their limited inclusion in clinical trials. Physiologic changes during pregnancy and lactation and growth and maturation of children alter pharmacokinetics (PK) and pharmacodynamics (PD) of drugs. Precision therapy in these populations requires knowledge of these effects. Efforts to enhance maternal and pediatric participation in clinical studies have increased over the past few decades. However, studies supporting precision therapeutics in these populations are often small and, in isolation, may have limited impact. Integration of data from various studies, for example through physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling or bioinformatics approaches, can augment the value of data from these studies, and help identify gaps in understanding. To catalyze research in maternal and pediatric precision therapeutics, the Obstetric and Pediatric Pharmacology and Therapeutics Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) established the Maternal and Pediatric Precision in Therapeutics (MPRINT) Hub. Herein, we provide an overview of the status of maternal-pediatric therapeutics research and introduce the Indiana University-Ohio State University MPRINT Hub Data, Model, Knowledge and Research Coordination Center (DMKRCC), which aims to facilitate research in maternal and pediatric precision therapeutics through the integration and assessment of existing knowledge, supporting pharmacometrics and clinical trials design, development of new real-world evidence resources, educational initiatives, and building collaborations among public and private partners, including other NICHD-funded networks. By fostering use of existing data and resources, the DMKRCC will identify critical gaps in knowledge and support efforts to overcome these gaps to enhance maternal-pediatric precision therapeutics.
孕产妇和儿科人群由于在临床试验中纳入有限，因此在历史上被认为是“治疗孤儿”。妊娠和哺乳期的生理变化以及儿童的生长和成熟改变了药物的药代动力学（PK）和药效动力学（PD）。这些人群的精准治疗需要了解这些影响。在过去几十年中，人们努力增加孕产妇和儿科人群参与临床研究的机会。然而，支持这些人群精准治疗的研究通常规模较小，孤立地看，可能影响有限。通过生理药代动力学/药效动力学（PBPK/PD）建模或生物信息学方法等各种研究数据的整合，可以增加这些研究数据的价值，并有助于确定理解上的差距。为了促进孕产妇和儿科精准治疗的研究，儿科学与生殖药理学和治疗学处（Eunice Kennedy Shriver 国家儿童健康与人类发育研究所（NICHD））设立了孕产妇和儿科精准治疗（MPRINT）中心。在此，我们概述了孕产妇儿科治疗学研究的现状，并介绍了印第安纳大学-俄亥俄州立大学 MPRINT 中心数据、模型、知识和研究协调中心（DMKRCC），该中心旨在通过整合和评估现有知识、支持药代动力学和临床试验设计、开发新的真实世界证据资源、开展教育计划以及建立公私合作伙伴之间的合作，促进孕产妇和儿科精准治疗的研究，包括其他 NICHD 资助的网络。通过促进现有数据和资源的使用，DMKRCC 将确定知识的关键差距，并支持克服这些差距的努力，以加强孕产妇儿科精准治疗。
