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: 10704756
• 负责人: MARY F PAINE
• 金额: $ 213.62万
• 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/10704756
• 关键词: Address; Archives; Biological; Biological Markers; Charge; Chemicals; Clinical; Clinical Pharmacology; Collaborations; Communication; Communities; Data; Data Analyses; Discipline; Documentation; Drug Interactions; Drug Kinetics; Educational workshop; Elderly; Ensure; Fostering; Goals; Growth; Health; Health Benefit; Human; In Vitro; Individual; Informatics; Information Management; Infrastructure; International; Investigation; Journals; Knowledge; Leadership; Manuscripts; Marketing; Methods; Mission; Modeling; Natural Product Drug; Natural Products; Natural Products Chemistry; Online Systems; Pharmaceutical Preparations; Pharmacology; Physiological; Population Heterogeneity; Procedures; Process; Public Health; Publishing; Qualifying; Records; Reproducibility; Research; Research Design; Research Personnel; Risk; Risk Assessment; Safety; Sales; Sampling; Science; Series; Source; Specimen; Thinking; Time; Update; Vulnerable Populations; archived data; 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 美国 NP 销售呈指数级增长。这项努力受到相对缺乏的药代动力学的挑战 对促进这些相互作用的单个 NP 成分的了解以及缺乏机制 了解 NP 对药物处置的影响。为解决这些知识差距而进行的 NPDI 调查 假定相同的 NP 的植物成分组成固有的巨大变异性使情况变得复杂， 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 来解决这一公共卫生问题。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传播带头解决这个问题 NPDI 研究特有的挑战。正如本续签申请中详细说明的那样，我们将推进该组织的使命 NaPDI 中心通过设计和执行新的机械驱动的交互项目，扩展了实用性 我们基于网络的数据存储库和公共门户网站，并将知识传播范围扩大到国家和地区 国际研究团体。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、分析学和信息学）和一个总体性的科学核心之间的关系 行政核心。药理学核心将扩展创新方法，选择三到五个高度优先的药物 NP 作为潜在具有临床意义的 NPDI 的沉淀剂进行研究。分析核心将来源并充分 表征市售的代表性 NP 的化学成分并提供 NP 研究 用于互动项目的材料不含掺假物和污染物。药理学核心将设计 并进行严格的体外研究，以确定 NP 对药物处置的影响机制；预测 使用基于生理学的药代动力学建模和模拟来确定 NPDI 的大小；和设计和 进行临床 NPDI 研究。分析核心将提供目标药物、NP 的定量分析 人体药代动力学样品中的成分和新兴药物处置生物标志物。所解释的 交互项目生成的数据将转移到开发和维护的数据存储库中 由信息学核心。主要发现将传播给科学界和其他感兴趣的社区 通过我们由信息学核心延续的独特的公共访问门户网站。所有核心将分担任务 通过在国家和国际上举办有针对性的讲习班和研讨会来扩大中心的外展活动 科学会议。由核心领导和 NCCIH 官员组成的指导委员会将共同监督 由 NCCIH 选出的相关领域专家组成的外部顾问小组负责中心科学进展。

项目成果

Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult Participants.

健康成人参与者中细胞色素 P450 介导的大麻素-药物相互作用的评估。

• DOI: 10.1002/cpt.2973
• 发表时间: 2023
• 期刊: Clinical pharmacology and therapeutics
• 影响因子: 6.7
• 作者: Bansal,Sumit;Zamarripa,CAustin;Spindle,ToryR;Weerts,EliseM;Thummel,KennethE;Vandrey,Ryan;Paine,MaryF;Unadkat,JashvantD
• 通讯作者: Unadkat,JashvantD

Chemical composition and biological effects of kratom (Mitragyna speciosa): In vitro studies with implications for efficacy and drug interactions.

• DOI: 10.1038/s41598-020-76119-w
• 发表时间: 2020-11-05
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Todd DA;Kellogg JJ;Wallace ED;Khin M;Flores-Bocanegra L;Tanna RS;McIntosh S;Raja HA;Graf TN;Hemby SE;Paine MF;Oberlies NH;Cech NB
• 通讯作者: Cech NB

An evaluation of adverse drug reactions and outcomes attributed to kratom in the US Food and Drug Administration Adverse Event Reporting System from January 2004 through September 2021.

• DOI: 10.1111/cts.13505
• 发表时间: 2023-06
• 期刊: Clinical and translational science

Clinical Relevance of Hepatic and Renal P-gp/BCRP Inhibition of Drugs: An International Transporter Consortium Perspective.

• DOI: 10.1002/cpt.2670
• 发表时间: 2022-09
• 期刊: CLINICAL PHARMACOLOGY & THERAPEUTICS
• 影响因子: 6.7
• 作者: Taskar, Kunal S.;Yang, Xinning;Neuhoff, Sibylle;Patel, Mitesh;Yoshida, Kenta;Paine, Mary F.;Brouwer, Kim L. R.;Chu, Xiaoyan;Sugiyama, Yuichi;Cook, Jack;Polli, Joseph W.;Hanna, Imad;Lai, Yurong;Zamek-Gliszczynski, Maciej
• 通讯作者: Zamek-Gliszczynski, Maciej

A New Data Repository for Pharmacokinetic Natural Product-Drug Interactions: From Chemical Characterization to Clinical Studies.

• DOI: 10.1124/dmd.120.000054
• 发表时间: 2020-10
• 期刊: Drug metabolism and disposition: the biological fate of chemicals
• 作者: Birer-Williams C;Gufford BT;Chou E;Alilio M;VanAlstine S;Morley RE;McCune JS;Paine MF;Boyce RD
• 通讯作者: Boyce RD