Low-dose buccal buprenorphine: Relative abuse potential and postoperative analgesic acceptability

低剂量含服丁丙诺啡：相对滥用潜力和术后镇痛可接受性

基本信息

批准号：
10572350
负责人：
Daniel Larach
金额：
$ 17.56万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-03-15 至 2028-02-29
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10572350
关键词：
Absence of pain sensation Acute Pain Address Adverse effects American Analgesics Authorization documentation Biometry Buprenorphine Caring Cessation of life Chad Clinical Clinical Investigator Clinical Sciences Clinical Trials Design Crossover Design Data Development Development Plans Diagnosis Dose Drug Prescriptions Drug abuse Enrollment Euphoria Exposure to FDA approved Formulation Friends Funding Iatrogenesis Intravenous Journals Knowledge Learning Light Mentors Observational Study Operative Surgical Procedures Opioid Opioid agonist Oral Overdose Oxycodone Pain Pain management Participant Patients Pattern Pharmaceutical Preparations Pharmacodynamics Phenotype Physicians Placebos Positioning Attribute Positive Reinforcements Postoperative Pain Postoperative Period Psychophysics Psychosocial Factor Publications Randomized Randomized, Controlled Trials Reporting Research Training Risk Seminal Sensory Shapes Specialist Standardization Testing Training Translational Research United States National Institutes of Health Ventilatory Depression Veterans Work abuse liability acceptability and feasibility antagonist authority career career development chronic pain clinical database clinical pain design disorder risk experience feasibility testing follow-up indexing insight mu opioid receptors opioid abuse opioid misuse opioid mortality opioid overdose opioid use opioid use disorder overdose risk participant enrollment prescription opioid prescription opioid misuse psychosocial randomized, clinical trials response risk/benefit ratio skills translational scientist translational study

项目摘要

ABSTRACT About 25% of the 69,710 U.S. opioid overdose deaths in 2020 involved prescription opioids directly, and many of the remaining overdose victims started opioid use with prescribed medication. Post-surgical opioid prescribing comprises an increasing share of opioid prescribing, with considerable risks for misuse, new persistent opioid use (NPOU), and opioid use disorder (OUD). There is a need to decrease these iatrogenic risks without compromising postoperative analgesia. Buccal buprenorphine represents a potential alternative to traditional post-surgical opioid prescribing with known lower respiratory depression risk. However, minimal data exists regarding whether its administration yields: (1) decreased abuse potential or (2) acceptable analgesia for acute pain. The Research Training Plan addresses these key gaps in understanding regarding the risk/benefit ratio of postoperative buccal buprenorphine. Aim 1 involves pharmacodynamic and psychophysical assessment of abuse potential and analgesia following buccal buprenorphine administration in a controlled experimental setting. Aim 2 entails a preliminary study assessing the feasibility and acceptability of a randomized clinical trial of prescribing buccal buprenorphine for postoperative pain management. In each aim, buccal buprenorphine will be compared with oxycodone, a commonly prescribed postoperative opioid. The candidate has prior experience with small observational studies and large clinical database studies related to post-surgical opioids and pain, with several first- and co-first-author publications in major journals. The Career Development Plan will allow him to gain new proficiencies in the assessment of abuse potential and pain as well as clinical trial design and execution, biostatistics, grantsmanship, and professional development. Mentor Dr. Stephen Bruehl specializes in the experimental assessment of the subjective and analgesic response to opioid administration. Co-mentor Dr. Sharon Walsh performed the seminal studies on buprenorphine pharmacodynamics and is an expert on OUD. Co-mentors Dr. Chad Brummett and Dr. David Edwards are authorities on postoperative opioid prescribing, and co-mentor Dr. Benjamin French is a specialist in clinical trial design and biostatistics. Vanderbilt’s setting is highly conducive to research training and implementation. This project will set the candidate on course for a career as an independent translational and clinical investigator. The proposed studies promise to offer insights into whether buccal buprenorphine can serve as an alternative postoperative analgesic with lower abuse potential. The subsequent planned definitive trial could reshape post-surgical opioid prescribing patterns.

抽象的 2020 年，美国 69,710 例阿片类药物过量死亡中，约 25% 直接涉及处方阿片类药物，而且许多其余的过量服用阿片类药物的受害者在术后开始使用阿片类药物。处方中阿片类药物处方的比例越来越大，滥用风险相当大，新持续性阿片类药物使用（NPOU）和阿片类药物使用障碍（OUD）需要减少这些医源性。在不影响术后镇痛的情况下降低风险。颊含丁丙诺啡是一种潜在的替代品。传统的术后阿片类药物处方已知较低的呼吸抑制风险，但数据很少。存在关于其给药是否产生：（1）降低滥用可能性或（2）可接受的镇痛效果研究培训计划解决了对风险/收益的理解上的这些关键差距。目标 1 涉及药效学和心理物理学。在受控情况下颊含丁丙诺啡给药后的滥用可能性和镇痛评估目标 2 需要进行初步研究，评估可行性和可接受性。开出颊含丁丙诺啡用于术后疼痛管理的随机临床试验在每个目标中，含服丁丙诺啡将与羟考酮（一种术后常用阿片类药物）进行比较。候选人之前具有与以下相关的小型观察研究和大型临床数据库研究的经验术后阿片类药物和疼痛，在主要期刊《职业》上发表了几篇第一作者和共同第一作者的论文。发展计划将使他能够在评估滥用潜力和疼痛方面获得新的熟练程度以及临床试验设计和执行、生物统计学、资助和专业发展。 Stephen Bruehl 博士专门从事主观和镇痛反应的实验评估联合导师 Sharon Walsh 博士对丁丙诺啡进行了开创性研究。 Chad Brummett 博士和 David Edwards 博士是药效学领域的专家。术后阿片类药物处方权威，共同导师 Benjamin French 博士是临床专家试验设计和生物统计学的环境非常有利于研究培训和实施。该项目将使候选人走上独立翻译和临床医生的职业道路研究者提出的研究有望为口含丁丙诺啡是否可以起到作用提供见解。随后计划的最终试验可能会出现一种替代性术后镇痛剂，其滥用可能性较低。重塑术后阿片类药物处方模式。