Clinical Importance of Drug-Drug Interactions

药物相互作用的临床重要性

• 批准号: 8658349
• 负责人: Sean Hennessy
• 金额: $ 47.17万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-15 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8658349
• 关键词: Address; Affect; Age; Agreement; Anticoagulation; Antidiabetic Drugs; Appearance; Attenuated; Award; Biological; Characteristics; Clinical; Coagulation Process; Collaborations; Cytochrome P450; Data; Data Set; Databases; Development; Drug Interactions; Drug Kinetics; Elderly; Esomeprazole; Event; Fenofibrate; Fibrates; Frequencies; Future; Gemfibrozil; Glipizide; Glyburide; Goals; Grant; Hemorrhage; Hypoglycemia; Impact evaluation; In Vitro; Indiana; International Normalized Ratio; Ischemic Stroke; Knowledge; Lansoprazole; Lipids; Lovastatin; Marketing; Measures; Medicare/Medicaid; Metabolism; Monitor; Omeprazole; Oral; Outcome; P-Glycoprotein; Patients; Pharmaceutical Preparations; Pioglitazone; Polypharmacy; Population; Population Database; Population Study; Pravastatin; Process; Proton Pump Inhibitors; Public Health; Recommendation; Research; Risk; Science; Series; Serum; Simvastatin; Source; Structure; Sulfonylurea Compounds; Thromboembolism; Time; Uncertainty; Universities; Update; Venous; Warfarin; atorvastatin; base; clinical effect; clopidogrel; computerized; diabetic; fluvastatin; gastrointestinal; glucose monitor; human CYP2C9 protein; in vivo; indexing; innovation; interdisciplinary collaboration; interest; medical schools; population based; programs; risk mitigation; rosuvastatin; symposium; tool

DESCRIPTION (provided by applicant): Drug-drug interactions (DDIs) are a significant clinical and public health burden, especially for older adults. This burden will increase further as the population ages and the degree of polypharmacy increases. Knowledge about DDIs comes from many sources, with rigorous population-based studies of clinical outcomes providing the most clinically useful information. Because very few population DDI studies have been performed, there is profound disagreement among the DDI compendia about which drug pairs cause clinically important DDIs. Further, uncertainty about which potential DDIs are clinically important has hampered efforts to mitigate the effects of DDIs, such as computerized decision support. Population studies of the clinical effects of DDIs are therefore badly needed, and should be integrated with research on the biological basis of DDIs. In this renewal application, we propose to extend our approach to population DDI studies in two important and innovative ways: 1) by actively and explicitly incorporating mechanistic considerations; and 2) by implementing a sequential approach of initially identifying and quantifying risk, then, where warranted based on this step, characterizing important DDIs further, with the goal of providing the basis for future efforts to mitigate risk. Based on an extensive and structured consultative process to identify research foci, we propose to conduct a series of population DDI studies using a large 5-state Medicaid/Medicare dataset. These studies will examine hypothesized interactions involving lipid lowering drugs, anti-clotting drugs, and oral anti-diabetic drugs, three drug classes with enormous relevance for older adults, and with high potential for causing clinically important DDIs. Thus, we will study potential DDIs of great clinical and public health importance, especially to older adults, and in the process develop data that will help elucidate the mechanisms of these potential DDIs.

描述（由申请人提供）：药物间相互作用（DDI）是一个重大的临床和公共卫生负担，尤其是对老年人。随着人口老龄化和多种药物使用程度的增加，这一负担将进一步增加。关于DDI的知识来自许多来源，严格的基于人群的临床结局研究提供了最有临床价值的信息。由于很少进行人群DDI研究，DDI药典中关于哪些药物对会引起临床重要DDI存在深刻分歧。此外，不确定哪些潜在DDI具有临床重要性 阻碍了减轻DDI影响的努力，例如计算机化的决策支持。因此，迫切需要对DDI的临床效果进行人群研究，并应与DDI的生物学基础研究相结合。 在本次更新申请中，我们建议以两种重要且创新的方式将我们的方法扩展到人群DDI研究：1）通过积极明确地纳入机制考虑因素; 2）通过实施一种顺序方法，首先识别和量化风险，然后在此步骤的基础上，进一步表征重要的DDI，为未来减轻风险的努力提供基础。 基于广泛和结构化的协商过程，以确定研究重点，我们建议进行一系列人口DDI研究，使用大型5个州的医疗补助/医疗保险数据集。这些研究将检查涉及降脂药物、抗凝药物和口服抗糖尿病药物的假设相互作用，这三类药物与老年人具有巨大的相关性，并且很有可能引起临床重要的DDI。 因此，我们将研究具有重要临床和公共卫生意义的潜在DDI，特别是对老年人，并在此过程中开发有助于阐明这些潜在DDI机制的数据。