Pharmacology Core

药理学核心

基本信息

批准号：
10254443
负责人：
MARY F PAINE
金额：
$ 68.86万
依托单位：
WASHINGTON STATE UNIVERSITY
依托单位国家：
美国
项目类别：
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/10254443
关键词：
Adopted Adult Biological Markers Black Pepper Botanicals Cannabinoids Carrier Proteins Cinnamon - dietary Clinical Clinical Research Clinical assessments Collaborations Companions Data Data Analyses Disease Drug Interactions Drug Kinetics Drug Prescriptions Drug Transport Echinacea purpurea Elderly Ensure Enzymes Evaluation Funding Future Goals Goldenseal Grant Green tea Health Benefit Hemp Human In Vitro Informatics Kinetics Lead Leadership Learning Licorice Methodology Methods Mitragyna Modeling Natural Product Drug Natural Products Natural Selections Patients Pharmaceutical Chemistry Pharmaceutical Preparations Pharmacology Physiological Population Procedures Process Public Health Publications Research Research Methodology Research Personnel Risk Sales Source System Toxicology United States Food and Drug Administration Vulnerable Populations Work aging population base bench to bedside clinically relevant clinically significant data dissemination data repository design drug disposition drug metabolism experience gut microbiota healthy volunteer in vivo inhibitor/antagonist innovation models and simulation novel pharmacokinetic model recruit research clinical testing response side effect success synergism therapy outcome tool vigilance volunteer web site

项目摘要

PROJECT SUMMARY OF THE PHARMACOLOGY CORE Sales of botanical and other natural products (NPs) continue to rise exponentially, increasing concerns for adverse interactions between NPs and concomitant prescription medications. During the first four-plus years of our Center of Excellence for Natural Product Drug Interaction Research (NaPDI Center), the Pharmacology Core established a framework for the selection, prioritization, and evaluation of high impact NPs as precipitants of potential clinically significant pharmacokinetic NP-drug interactions (NPDIs) that could lead to suboptimal therapeutic outcomes. We adopted a rigorous, systematic ‘predict, learn, and confirm’ approach involving robust human-relevant in vitro systems, pharmacokinetic modeling and simulation, and clinical evaluation to assess the clinical relevance of NPDIs. The Pharmacology Core component of this renewal application proposes three SPECIFIC AIMS that refine and extend the ‘best practices’ developed during the initial funding period. AIM 1: the Pharmacology Core, in collaboration with the Analytical Core, Informatics Core, Administrative Core, and Steering Committee, will select and prioritize three to five widely used NPs as precipitants of potential clinically significant NPDIs using our established method termed the fulcrum model. Based on our experience to date, we have expanded this innovative model to include a fast track option that accommodates emerging NPs with heightened NPDI risk to remain responsive to public health needs. The following high priority NPs are proposed: kratom, hemp products, cinnamon, black pepper supplement, and the combination product Echinacea purpurea/goldenseal. AIM 2: the Pharmacology Core will evaluate the NPDI liability of these NPs using established human in vitro systems for both drug metabolizing enzyme and transporter activity and in vitro to in vivo extrapolation approaches recommended by the Food and Drug Administration. AIM 3: the Pharmacology Core will evaluate the clinical NPDI risk in healthy volunteers that will include a more vulnerable, elderly population. The rationale for targeting the latter group is that specific NPs are increasingly marketed to the aging population, often claiming fewer side effects than prescription medications. The Pharmacology Core’s clinical research capabilities are a cornerstone of the NaPDI Center, having completed five clinical studies during the initial funding period. Throughout the proposed project, NPs that emerge from companion R21 grants will be applied to our expanded fulcrum model and potentially advanced to our NP list. We will continually integrate new clinical research methods, such as evaluating the effects of the gut microbiota and incorporating transporter probe cocktails and biomarkers of drug metabolizing enzymes and transporters. The Pharmacology Core, in synergy with the other Cores of the NaPDI Center, has efficiently and definitively established a new standard for NPDI research. Capitalizing on the momentum of our world class team, we are confident to continue this trajectory by innovating additional recommended approaches for NPDI research and identifying novel clinically relevant NPDIs.

药理学核心项目摘要植物和其他天然产品 (NP) 的销量继续呈指数级增长，增加了人们的担忧 NP 与伴随处方药之间的不良相互作用在最初四年多的时间里。我们的天然产物药物相互作用研究卓越中心（NaPDI 中心）、药理学 Core 建立了一个框架，用于选择、优先排序和评估作为沉淀剂的高影响力纳米颗粒潜在的具有临床意义的药代动力学 NP-药物相互作用 (NPDI) 可能导致次优我们采用了严格、系统的“预测、学习和确认”方法，涉及稳健的治疗结果。与人体相关的体外系统、药代动力学建模和模拟以及临床评估以评估该更新申请的药理学核心部分提出了三个相关性。细化和扩展初始资助期间制定的“最佳实践”的具体目标 1：药理学核心，与分析核心、信息学核心、管理核心和指导委员会将选择并优先考虑三到五种广泛使用的纳米粒子作为潜在临床的促进剂根据我们迄今为止的经验，我们使用我们既定的方法（称为支点模型）来计算显着的 NPDI。扩展了这一创新模式，包括一个快速通道选项，可容纳新兴的 NP 为了保持对公共卫生需求的响应，存在重大 NPDI 风险建议采取以下高度优先的 NP：卡痛叶、大麻产品、肉桂、黑胡椒补充剂以及组合产品紫锥菊 purpurea/goldenseal AIM 2：药理学核心将使用这些 NP 来评估 NPDI 责任。建立了人体体外药物代谢酶和转运蛋白活性系统以及体外到体内美国食品和药物管理局推荐的体内外推方法 AIM 3：药理学。 Core 将评估健康志愿者的临床 NPDI 风险，其中包括更脆弱的老年人针对后一群体的理由是，特定的纳米颗粒越来越多地面向老年人群。药理学核心的临床研究通常声称副作用更少。研究能力是 NaPDI 中心的基石，在该中心完成了五项临床研究在整个拟议项目的初始资助期间，来自配套 R21 赠款的 NP 将得到资助。应用于我们扩展的支点模型，并可能进入我们的 NP 列表，我们将不断集成新的。临床研究方法，例如评估肠道微生物群的影响和整合转运蛋白药物代谢酶和转运蛋白的探针混合物和生物标志物，《药理学核心》。与 NaPDI 中心其他核心的协同作用，有效、明确地建立了新的标准借助我们世界一流团队的势头，我们有信心继续开展这项研究。通过创新 NPDI 研究的其他推荐方法并确定新的临床方法来跟踪轨迹相关 NPDI。