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: 9386165
• 负责人: Jeannine S McCune
• 金额: $ 28.45万
• 依托单位: UNIVERSITY OF WASHINGTON
• 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 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9386165
• 关键词: Address; Archives; Clinical; Clinical Management; Clinical assessments; Collaborations; Communication; Communities; Complement; Computer Simulation; Data; Databases; Decision Trees; Drug Interactions; Drug Kinetics; Drug usage; Ensure; Future; Goals; Health; Healthcare; Human; In Vitro; Individual; Informatics; Investigation; Knowledge; Leadership; Literature; Methods; Names; National Center for Complementary and Alternative Medicine; Natural Product Drug; Natural Products; Natural Products Chemistry; Nature; Online Systems; Pharmaceutical Preparations; Pharmacology; Physiological; Procedures; Process; Quality Control; Research; Research Infrastructure; Research Personnel; Risk; Safety; Sales; Sampling; Series; Source; Vulnerable Populations; Work; base; clinical risk; clinically relevant; data archive; design; experience; improved; in vivo; innovation; liquid chromatography mass spectrometry; models and simulation; multidisciplinary; novel; operation; perpetrators; pharmacokinetic model; public health relevance; quality assurance; repository; web portal

 DESCRIPTION (provided by applicant): As natural products (NP) sales increase, the risk of adverse NP-drug interactions (NPDIs) increases, yet the pharmacokinetic (PK) elucidation and clinical relevance of putative NPDIs remain elusive. Assessing the risk of NPDIs is more challenging than that of drug-drug interactions (DDIs), often due to relatively scant PK knowledge of individual NP constituents that perpetrate these interactions. The proposed U54 Center will develop a roadmap for NPDI research through a series of well-designed human in vitro and in vivo studies (termed Interaction Projects) on 4-6 priority NPs that pose a potential risk for clinically relevant NPDIs. A repository will be developed for the data generated from the Interaction Projects, and results will be communicated to various target audiences through a public portal. This U54 Center is composed of an accomplished team of investigators, including pharmacokineticists with expertise in NPDIs, complemented by expertise in NP chemistry, DDIs, and health information communication. In collaboration with the Steering Committee, an innovative strategy that combines a mechanistic approach with practical considerations (e.g., popularity of the NPs) will be used to select and prioritize 4-6 NPs for further investigation in te Interaction Projects. Mechanistic aspects include curated clinical NDPI data from the widely used Drug Interaction Database (DIDB) of the Informatics Core, structural alerts, and compelling preliminary clinical and in silico NPDI data. Once selected, the NPs will be entered into a Decision Tree for assessment of NPDI liability and probable significance of interactions with victim drugs. In parallel, the Pharmacology Core will develop detailed Statements of Work for the human in vitro and in vivo studies - while the Analytical Core will source, acquire, and characterize the selected NPs - for the Interaction Projects. Upon completion of each project, the Analytical Core will analyze the PK samples, and the Pharmacology Core will develop physiologically-based PK models for further assessment of the clinical relevance of the Interaction Project results. Throughout these projects, the Informatics Core will create a data repository embedded within a public portal web-based application named, NaPDI app, for Natural Product-Drug Interaction application. The repository, built using the DIDB framework, will allow researchers to access both raw data and summarized results. The U54 Center will also develop and share Best Practices recommended for the conduct of NPDI studies, based on the experience with and results from the Interaction Projects, with the research communities via the public portal. Effective dissemination of the Interaction Project results will be ensured through user experience and brand content studies with target audiences - researchers/practitioners and lay public - to refine the public portal content. The Informatics Core will ensure that the U54 Center's results are archived, organized, analyzed, and well-publicized, allowing for improved design of future NPDI research and ultimately, improved decisions on the optimal management of clinically relevant NPDIs.

 描述（由适用提供）：随着天然产品（NP）销售的增加，不良NP-rug相互作用（NPDIS）的风险增加，但推定NPDIS的药代动力学（PK）阐明和临床相关性仍然难以捉摸。评估NPDI的风险比药物相互作用（DDI）更具挑战性，这通常是由于PK对单个NP成分的知识相对很少而导致这些相互作用。拟议的U54中心将通过一系列精心设计的人体体外和体内研究（称为相互作用项目）在4-6优先NP上开发NPDI研究的路线图，这些NP对临床相关的NPDI有潜在的风险。将为从交互项目生成的数据开发一个存储库，并将通过公共门户将结果传达给各种目标受众。这个U54中心由一支成熟的研究人员组成，其中包括由NPDIS专家的药代动力学家，由NP Chemistry，DDIS和健康信息通信的专家完成。与指导委员会合作，将机械方法与实际考虑（例如，NP的受欢迎程度）相结合的创新战略将用于选择和优先级4-6 NP，以在TE交互项目中进行进一步调查。机械方面包括来自信息核心的广泛使用的药物相互作用数据库（DIDB）的临床NDPI数据，结构警报和引人注目的初步临床和硅NPDI数据。一旦选择，NP将进入决策树，以评估NPDI责任和与受害者药物相互作用的有问题意义。同时，药理学核心将为人类体外和体内研究开发详细的工作陈述 - 而分析核心将为相互作用项目提供，获取和表征所选的NP。每个项目完成后，分析核心将分析PK样品，药理学核心将开发基于物理的PK模型，以进一步评估相互作用项目结果的临床相关性。在这些项目中，Informatics Core将创建一个数据存储库，该数据存储库嵌入了基于公共门户网站的NAPDI应用程序中，用于自然产品 - 毒品交互应用程序。使用DIDB框架构建的存储库将允许研究人员访问原始数据和汇总结果。 U54中心还将根据互动项目的经验和结果以及通过公共门户网站与研究社区的经验和结果开发和共享建议进行NPDI研究的最佳实践。通过与目标受众（研究人员/从业人员和公众）的用户体验和品牌研究来确保对交互项目结果的有效传播，以完善公共门户网站内容。信息学核心将确保U54中心的结果被归档，组织，分析和广泛发布，从而改善了未来NPDI研究的设计，并最终改进了对临床相关NPDIS的最佳管理的改进决策。