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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.

药理学核心项目总结