Natural Product-Drug Interaction Research: The Roadmap to Best Practices

整个U 54中心的项目概要 评估不良天然产物（NP）-药物相互作用（NPDI）的风险至关重要，因为 NP在美国的销售呈指数级增长。这一努力受到相对缺乏的药代动力学的挑战 知识的个别NP成分沉淀这些相互作用和缺乏机制 了解NP对药物处置的影响。为弥补这些知识差距而开展的国家产品和服务指数调查如下： 被假定相同NP的植物成分组成的固有的大的可变性所复杂化， 获得足够的高质量NP研究材料，以及NP销售的不同人群， 包括老年人。我们建立的天然产物药物相互作用研究卓越中心 （NaPDI中心）由国家补充和综合健康中心（NCCIH）于2015年创建 来解决这个公共卫生问题。由临床专家组成的跨学科研究团队 药理学，NP化学，生物医学信息学和健康通信领导的费用，以解决 NPDI研究所面临的独特挑战。正如本更新申请中详细说明的那样，我们将推进 NaPDI中心通过设计和执行新的机械驱动的互动项目，扩大实用性 我们的网络数据储存库和公共门户网站，并扩大知识传播到国家和 国际研究社区。这些活动将通过协同互动来完成 三个既定的科学核心（药理学，分析和信息学）和一个总体的 行政核心。药理学核心将扩大一种创新的方法，以选择三到五个高优先级 NP作为潜在临床显著NPDI的沉淀物进行研究。分析核心将提供 表征市售代表性NP的化学组成，并提供NP研究 为互动项目提供不含掺杂物和污染物的材料。药理学核心将设计 并进行严格的体外研究，以建立NP对药物处置的作用机制;预测 使用基于生理学的药代动力学建模和模拟， 进行临床NPDI研究。分析核心将提供目标药物NP的定量分析 在人体药代动力学样品中，药物成分和新出现的药物处置生物标志物。经解释的 从交互项目中产生的数据将被传输到开发和维护的数据存储库中 信息学核心将向科学界和其他感兴趣的团体传播主要的调查结果 通过我们独特的公共访问门户网站信息学核心永存。所有核心将分担任务 通过在国家和国际各级举办有针对性的讲习班和专题讨论会， 科学会议。由核心领导人和NCCIH官员组成的指导委员会将共同监督 中心的科学进展与外部咨询小组的专家在相关领域的NCCIH选择。

PROJECT SUMMARY OF THE OVERALL U54 CENTER Assessing the risk of adverse natural product (NP)-drug interactions (NPDIs) is of paramount importance due to the exponential NP sales growth in the US. This effort is challenged by relatively scant pharmacokinetic knowledge of individual NP constituents that precipitate these interactions and a lack of mechanistic understanding of NP effects on drug disposition. Investigations of NPDIs to address these knowledge gaps are complicated by the inherently large variability in phytoconstituent composition of supposedly the same NP, acquisition of sufficient high-quality NP study materials, and the diverse populations to which NPs are marketed, including the elderly. Our established Center of Excellence for Natural Product Drug Interaction Research (NaPDI Center) was created by the National Center for Complementary and Integrative Heath (NCCIH) in 2015 to address this public health problem. A cross-disciplinary research team composed of experts in clinical pharmacology, NP chemistry, biomedical informatics, and health communications led the charge to address the challenges unique to NPDI research. As detailed in this renewal application, we will advance the mission of the NaPDI Center by designing and executing new mechanistically-driven Interaction Projects, expanding the utility of our web-based data repository and public portal, and broadening dissemination of knowledge to national and international research communities. These activities will be accomplished through synergistic interactions between three established scientific Cores (Pharmacology, Analytical, and Informatics) and an overarching Administrative Core. The Pharmacology Core will expand an innovative method to select three to five high priority NPs to study as precipitants of potential clinically significant NPDIs. The Analytical Core will source and fully characterize the chemical composition of commercially available, representative NPs and provide NP study materials free of adulterants and contaminants for the Interaction Projects. The Pharmacology Core will design and execute rigorous in vitro studies to establish the mechanism of NP effects on drug disposition; predict the magnitude of NPDIs using physiologically-based pharmacokinetic modeling and simulation; and design and conduct clinical NPDI studies. The Analytical Core will provide quantitative analysis of object drugs, NP constituents, and emerging drug disposition biomarkers in the human pharmacokinetic samples. The interpreted data generated from the Interaction Projects will be transferred to the data repository developed and maintained by the Informatics Core. Major findings will be disseminated to scientific and other interested communities through our unique public access web portal perpetuated by the Informatics Core. All Cores will share the task of broadening Center outreach activities through targeted workshops and symposia at national and international scientific meetings. A Steering Committee composed of Core leaders and NCCIH officials will jointly oversee Center scientific progress with an External Advisory Panel of experts in relevant fields selected by NCCIH.