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.

u54中心整体项目总结