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

天然产物-药物相互作用研究：最佳实践路线图

• 批准号: 10471289
• 负责人: MARY F PAINE
• 金额: $ 217.64万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10471289
• 关键词: Address; Archives; Biological; Biological Markers; Charge; Chemicals; Clinical; Clinical Pharmacology; Collaborations; Communication; Communities; Data; Discipline; Documentation; Drug Interactions; Drug Kinetics; Educational workshop; Elderly; Ensure; Fostering; Goals; Growth; Health; Health Benefit; Human; In Vitro; Individual; Informatics; Information Management; International; Investigation; Journals; Knowledge; Lead; Leadership; Manuscripts; Methods; Mission; Modeling; Natural Product Drug; Natural Products; Natural Products Chemistry; Online Systems; Pharmaceutical Preparations; Pharmacology; Physiological; Population Heterogeneity; Procedures; Process; Public Health; Publishing; Records; Reproducibility; Research; Research Activity; Research Design; Research Infrastructure; Research Personnel; Risk; Safety; Sales; Sampling; Science; Series; Source; Specimen; Thinking; Time; Update; Vulnerable Populations; archive data; archived data; base; biomedical informatics; clinically relevant; clinically significant; cost; data repository; design; drug disposition; experience; health communication; improved; innovation; interest; liquid chromatography mass spectrometry; meetings; models and simulation; outreach; pharmacokinetic model; public database; repository; success; symposium; therapy outcome; tool; web portal

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.

整个U54中心的项目摘要 评估不良天然产品（NP） - 药水相互作用（NPDI）的风险至关重要 美国的NP销售增长。相对较少的药代动力学挑战了这一努力 了解导致这些相互作用和缺乏机械性的单个NP成分的知识 了解NP对药物处置的影响。 NPDI以解决这些知识差距的调查是 由于据称是同一np的植物成分组成的固有变异性，因此很复杂 获取足够的高质量NP研究材料，以及NP销售的不同人群， 包括老人。我们既定的自然产品药物互动研究卓越中心 （NAPDI中心）由国家补充和综合卫生中心（NCCIH）于2015年创建 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导致该指控解决 NPDI研究独有的挑战。如本续订应用中所详细介绍的那样，我们将推进 NAPDI中心通过设计和执行新机械驱动的交互项目，扩大实用程序 我们基于网络的数据存储库和公共门户网站，并将知识传播给国家和 国际研究社区。这些活动将通过协同互动来完成 在三个既定的科学核心（药理学，分析和信息学）和总体之间 行政核心。药理学核心将扩展一种创新方法，以选择三到五个高优先级 NP作为潜在临床意义的NPDI的沉淀物进行研究。分析核心将充分来源 表征可商购的代表性NP的化学成分，并提供NP研究 没有用于互动项目的掺假剂和污染物的材料。药理学核心将设计 并执行严格的体外研究，以确定NP对药物处置的影响；预测 使用基于生理的药代动力学建模和仿真的NPDI的大小；和设计和 进行临床NPDI研究。分析核心将提供对象药物NP的定量分析 人类药代动力学样本中的成分和新兴的药物处置生物标志物。解释 从交互项目产生的数据将转移到开发和维护的数据存储库中 通过信息学核心。主要发现将被传播到科学和其他感兴趣的社区 通过我们独特的公共访问Web门户网站，由Informatics Core永久存在。所有核心都会分享任务 通过有针对性的研讨会和国际国际的针对性研讨会和研讨会来扩大中心外展活动 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 NCCIH选择的相关领域专家的外部咨询小组中心科学进步。