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

• 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
• 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

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.

摘要 在2020年美国69,710例阿片类药物过量死亡中，约有25%直接涉及处方阿片类药物，其中许多 其余的过量受害者开始使用阿片类药物和处方药物。手术后阿片类药物 处方包括越来越多的阿片类药物处方，有相当大的滥用风险，新的 阿片类药物持续使用(NPOU)和阿片使用障碍(OUD)。有必要减少这些医源性的 在不影响术后镇痛的情况下增加风险。丁丙诺啡是一种潜在的替代药物 手术后传统的阿片类药物处方具有已知的下呼吸抑制风险。然而，最低限度的数据 关于它的使用是否产生：(1)减少滥用可能性或(2)可接受的止痛 剧烈的疼痛。研究培训计划解决了在理解风险/收益方面的这些主要差距 术后口腔丁丙诺啡比例。目标1涉及药效学和心理物理学 丁丙诺啡口腔给药后滥用潜能和镇痛效果的评估 实验环境。目标2需要进行一项初步研究，评估一项 丁丙诺啡含片用于术后疼痛控制的随机临床试验。在每个目标中， 口腔丁丙诺啡将与羟考酮进行比较，羟考酮是术后常用的阿片类药物。这个 有相关的小型观察性研究和大型临床数据库研究经验 手术后阿片类药物和疼痛，在主要期刊上发表了几篇第一作者和联合第一作者的论文。职业生涯 发展计划将使他能够在评估滥用潜力和痛苦方面获得新的熟练程度，因为 以及临床试验设计和执行、生物统计学、专业技能和专业发展。门托 Stephen Bruehl博士专门从事主观和止痛反应的实验评估 阿片类药物的使用。共同导师莎伦·沃尔什博士对丁丙诺啡进行了开创性研究 他是药效学方面的专家。共同导师查德·布鲁米特博士和大卫·爱德华兹博士 术后阿片类药物处方权威，联合导师本杰明·弗伦奇博士是临床专家 试验设计和生物统计学。范德比尔特的背景非常有利于研究、培训和实施。 这个项目将使候选人的职业生涯作为一个独立的翻译和临床 调查员。拟议中的研究承诺为口腔丁丙诺啡是否可以作为 一种替代的术后止痛剂，滥用可能性较低。随后计划的最终审判可能会 重塑手术后阿片类药物的处方模式。