Drug-Drug Interactions Involving Methadone and Buprenorphine

涉及美沙酮和丁丙诺啡的药物相互作用

• 批准号: 10436942
• 负责人: Sean Hennessy
• 金额: $ 48.37万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10436942
• 关键词: ABCB1 gene; Absence of pain sensation; Accident and Emergency department; Acute; Address; Adverse effects; Age; Area; Biological; Blood Circulation; Buprenorphine; Case Series; Chronic; Clinical; Cytochrome P450; Dose; Drug Combinations; Drug Interactions; Drug Kinetics; Enzymes; Ethnic Origin; Etiology; Exposure to; Heart Arrest; Heterogeneity; Hospitalization; Individual; Investigation; Knowledge; Metabolism; Methadone; Methods; Neuraxis; Opioid; Patients; Persons; Pharmaceutical Preparations; Pharmacodynamics; Pharmacoepidemiology; Pharmacology; Pharmacotherapy; Physiological; Poisoning; Population; Property; Public Health; Race; Relapse; Research; Screening Result; Series; Subgroup; Therapeutic; Time; Transportation; Triad Acrylic Resin; Work; World Health; base; case control; clinically actionable; cohort; comorbidity; comparative safety; demographics; design; drug metabolism; experience; frailty; genetic variant; high throughput screening; innovation; insight; knowledge base; medication-assisted treatment; multidisciplinary; opioid epidemic; opioid overdose; opioid use disorder; pharmacokinetic model; pharmacokinetics and pharmacodynamics; response; screening; sex; treatment effect; webinar

A crucial component of the US response to the opioid epidemic is expanding the use of medication assisted treatment, most commonly using methadone or buprenorphine, for opioid use disorder. Many persons with opioid use disorder have comorbidities that necessitate treatment with other acutely and chronically used medications, and this proportion is expected to rise with the evolving demographics of the opioid epidemic. Methadone and buprenorphine have pharmaco- kinetic and pharmacodynamic properties that make them highly likely to interact adversely with many other drugs, some of which are very commonly used. Further, past experience demonstrates that existing pharmacologic knowledge is insufficient to predict all clinically important drug-drug interactions. Despite the high potential for and serious consequences of both predicted and unanticipated drug-drug interactions, almost no research has examined the real-world health effects of drugs given concomitantly with methadone or buprenorphine. This presents a striking knowledge gap with large and growing clinical and public health consequences. This project's broad objective is to produce clinically-actionable and biologically-relevant knowledge about which medications interact with methadone and/or buprenorphine. Our work will further elucidate interactions with regard to order of drug initiation, dose-response effects, duration-response effects, and susceptible populations. We will achieve these objectives by: a) performing high-throughput physiologically-based pharmacokinetic screening to predict the degree to which two-drug and three-drug combinations that include methadone or buprenorphine increase biological exposure to those agents; b) performing high-throughput pharmacoepidemiologic screening of two-drug and three-drug combinations that include methadone or buprenorphine with regard to rate of emergency department presentation or hospitalization for opioid overdose and poisoning, opioid adverse effects, and cardiac arrest; c) convening an independent multidisciplinary Expert Panel to review screening results and prioritize potential drug interaction pairs and triads for further investigation; and d) conduct a series of rigorous pharmacoepidemiologic studies to inform causal inferences and thereby generate clinically-actionable evidence on prioritized methadone and buprenorphine drug-drug interactions. This rigorous, innovative study will produce actionable results that will guide the selection of drug therapy in the growing population of persons using methadone or buprenorphine who have comorbidities necessitating treatment.

美国对阿片类药物流行的反应的关键组成部分正在扩大用药辅助治疗的使用， 最常见的是使用美沙酮或丁丙诺啡用于阿片类药物使用障碍。许多患有阿片类药物使用障碍的人患有 需要使用其他急性和长期使用药物治疗的合并症，这一比例是 预计随着阿片类药物流行的不断发展的人口统计学的增长。美沙酮和丁丙诺啡具有药物 动力学和药效学特性使它们高度可能与许多其他药物不利，有些药物相互作用 其中非常常用。此外，过去的经验表明，现有的药理学知识是 不足以预测所有临床上重要的药物相互作用。尽管有很高的潜力和严重的 预测和意外药物相互作用的后果，几乎没有研究检查现实世界 与美沙酮或丁丙诺啡同时给予的药物的健康作用。这是一个明显的知识差距 临床和公共卫生的影响很大。 该项目的广泛目标是产生临床上可靠和与生物学的知识 药物与美沙酮和/或丁丙诺啡相互作用。我们的工作将进一步阐明有关 药物启动，剂量反应效应，持续时间反应效应和易感人群的顺序。我们将实现 这些目标是：a）进行高通量生理生理的药代动力学筛查以预测程度 两种药物和三药组合包括美沙酮或丁丙诺啡增加的生物学暴露 那些特工； b）进行两次药物和三药组合的高通量药物筛查 关于急诊室介绍或住院率，包括美沙酮或丁丙诺啡 阿片类药物过量和中毒，阿片类药物的不良反应和心脏骤停； c）召集独立的多学科 专家小组审查筛查结果并确定潜在的药物相互作用对和三合会以进行进一步研究； d）进行一系列严格的药物ePIDEMIologic研究，以告知因果推断，从而产生 优先级美沙酮和丁丙诺啡药物相互作用的临床证据。严格， 创新研究将产生可行的结果，以指导在不断增长的人群中选择药物治疗 使用白沙酮或丁丙诺啡需要治疗的人。