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Drug-Drug Interactions Involving Methadone and Buprenorphine

涉及美沙酮和丁丙诺啡的药物相互作用

基本信息

批准号：
10205012
负责人：
Sean Hennessy
金额：
$ 64.75万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
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/10205012
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 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

项目摘要

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.

美国应对阿片类药物流行的一个关键组成部分是扩大药物辅助治疗的使用，