Pharmacology Core

药理学核心

• 批准号: 10471291
• 负责人: MARY F PAINE
• 金额: $ 78.42万
• 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/10471291
• 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; innovation; models and simulation; novel; pharmacokinetic model; recruit; research clinical testing; response; side effect; success; synergism; therapy outcome; tool; vigilance; volunteer; web site

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）的销售继续呈指数增长，对 NP与伴随的处方药之间的不良相互作用。在最初的四年 我们的天然产品药物互动研究卓越中心（NAPDI中心），药理学 核心建立了选择，优先级和评估高影响NP的框架 可能导致次优的药代动力学NP-rug相互作用（NPDI） 治疗结果。我们采用了一种严格，系统的“预测，学习和确认”方法，涉及强大 与人相关的体外系统，药代动力学建模和模拟以及临床评估以评估 NPDIS的临床相关性。该更新申请的药理学核心组成部分提案三个 精炼和扩展最初资金期间开发的“最佳实践”的具体目标。目标1： 药理学核心与分析核心，信息学核心，行政核心和 指导委员会将选择并优先考虑三到五个广泛使用的NP作为潜在的临床上的沉淀物 使用我们既定的方法称为Fulcrum模型的重要NPDI。根据我们迄今为止的经验，我们 已经扩展了这种创新模型，包括一个快速轨道选项，可容纳新兴的NP NPDI的风险增加了，以响应公共卫生需求。提出了以下高优先级NP： Kratom，大麻产品，肉桂，黑胡椒补充剂和组合产品紫锥菊 紫红色/金色。 AIM 2：药理学核心将使用这些NP的NPDI责任评估 建立了用于药物代谢酶和转运蛋白活性的人体体外系统以及体外 食品药品监督管理局建议采用的体内外推方法。目标3：药理学 核心将评估健康志愿者的临床NPDI风险，其中包括一个更脆弱的，较早的 人口。针对后来的小组的基本原理是，特定的NP越来越多地销售到衰老 人口通常比处方药更少的副作用。药理学核心的临床 研究能力是NAPDI中心的基石，在此期间完成了五项临床研究 初始资金期。通过拟议的项目，从伴侣R21赠款中出现的NP将是 应用于我们扩展的Fulcrum模型，并有潜在地推进我们的NP列表。我们将不断整合新的 临床研究方法，例如评估肠道菌群的影响并掺入转运蛋白 药物代谢酶和转运蛋白的探针鸡尾酒和生物标志物。药理学核心，在 与NAPDI中心其他核心的协同作用，有效，明确地建立了一个新标准 NPDI研究。利用我们世界一流团队的势头，我们有信心继续这一点 通过创新的其他推荐方法进行NPDI研究并在临床上识别新颖的轨迹 相关的npdis。