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.

抽象的 2020年美国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 在其余的过量滥用中，用处方药开始使用阿片类药物。手术后阿片类药物 处方包括越来越多的阿片类药物处方，对MISSUSE的考虑风险 持续的阿片类药物使用（NPOU）和阿片类药物使用障碍（OUD）。有必要降低这些医源性 风险而不会损害术后镇痛。颊丁丙诺啡代表了潜在的替代方案 传统的手术后阿片类药物处方，具有已知的下呼吸道抑郁症风险。但是，最小数据 有关其管理是否产生的存在：（1）滥用潜力降低或（2）可接受的镇痛 急性疼痛。研究培训计划解决了这些关键差距，以理解风险/利益 术后颊丁丙诺啡之比。 AIM 1涉及药效和心理物理 在受控 实验设置。 AIM 2需要进行初步研究，以评估 开处方颊丁丙诺啡的随机临床试验用于术后疼痛管理。在每个目标中， 颊丁丙诺啡将与羟考酮（一种通常开处方的术后阿片类药物）进行比较。这 候选人在小型观察研究和大型临床数据库研究方面具有先前的经验 术后阿片类药物和疼痛，在主要期刊上有几个第一和联合作者出版物。职业 发展计划将使他能够在评估虐待潜力和痛苦的评估中获得新的能力 以及临床试验设计和执行，生物统计学，赠款和专业发展。导师 斯蒂芬·布鲁尔（Stephen Bruehl）博士专门研究对主观和镇痛反应的实验评估 阿片类药物给药。副院士莎朗·沃尔什（Sharon Walsh）博士对丁丙诺啡进行第二项研究 药效学，是OUD的专家。乍得·布拉米特博士和大卫·爱德华兹博士是 术后阿片类药物处方的当局，同事Benjamin French博士是临床专家 试验设计和生物统计学。范德比尔特（Vanderbilt）的设置高度指导研究培训和实施。 该项目将使候选人成为独立翻译和临床的职业生涯 研究者。拟议的研究有望提供有关是否可以作为颊丁丙诺啡的见解 替代性饲养型镇痛药具有较低的虐待潜力。随后计划的权威审判可以 重塑外科治疗后处方模式。