Pharmacologically-based Strategies for Buprenorphine Treatment During Pregnancy

妊娠期丁丙诺啡治疗的药理学策略

• 批准号: 10152373
• 负责人: STEVE N CARITIS
• 金额: $ 66.71万
• 依托单位: MAGEE-WOMEN'S RES INST AND FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-17 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10152373
• 关键词: Acute; Address; Blood; Blood Pressure; Brain; Buprenorphine; Caliber; Caring; Cessation of life; Chronic; Clinical; Conflict (Psychology); Data; Development; Diagnosis; Dopamine; Dose; Drug Kinetics; Drug Metabolic Detoxication; Elements; Enrollment; Exposure to; Frequencies; Guidelines; Hair; Heart Rate; Hour; Infant; Investigation; Knowledge; Maternal Exposure; Measures; Meconium; Medical; Methadone; Monitor; Mothers; Neonatal; Neonatal Abstinence Syndrome; Neurotransmitters; Norepinephrine; Opiate Addiction; Opioid; Pharmaceutical Preparations; Pharmacodynamics; Pharmacology; Physiological; Placenta; Plasma; Pregnancy; Pregnant Women; Property; Prospective cohort; Psychosocial Assessment and Care; Questionnaires; Recovery; Regimen; Relapse; Risk; Serotonin; Severities; Stimulus; Supervision; Symptoms; System; Thinking; Time; Tissues; Umbilical cord structure; Withdrawal; Withdrawal Symptom; Woman; appropriate dose; base; buprenorphine treatment; clinical Diagnosis; cohort; craving; diagnostic accuracy; economic impact; fetal; high risk; improved; medication-assisted treatment; opioid use; opioid use disorder; opioid withdrawal; pharmacokinetic characteristic; pharmacokinetics and pharmacodynamics; pregnant; prenatal exposure; prescription opioid; programs; recruit; relapse risk; success; tool; treatment optimization; treatment program

Title: Pharmacologically-based Strategies for Buprenorphine Treatment During Pregnancy Abstract This proposal will challenge several current clinical approaches to managing the pregnant woman with an opioid use disorder. Dosing of buprenorphine (BUP) in pregnant women is based on studies in non-pregnant subjects which suggests that symptoms of withdrawal occur when plasma BUP concentrations are < 1ng/ml. No such data exist for pregnant women but this is a prerequisite for defining an appropriate dosing regimen of BUP in pregnant women. We will define his threshold by monitoring women undergoing mild, medically directed withdrawal. The Clinical Opioid Withdrawal Scale score and the Finnegan score for NAS are key to defining when withdrawal occurs and thus dictate treatment in mother and baby. Neither scoring system is based on plasma BUP concentrations and thus, may not reflect true opioid withdrawal. This proposal aims to develop physiologic based scoring systems that refine the accuracy of diagnosis and optimizes treatment. The risk of NAS is assumed to be unrelated to maternal or fetal exposure to opioids leading to a generous use of opioid medications in medication-assisted treatment (MAT) programs. This assumption is based on a few small studies with conflicting results. This relationship will be explored using a maternal and baby hair, placenta , cord and meconium as predictors of chronic maternal and fetal exposure as these are unaffected by maternal truthfulness or acute dosing at the time of delivery. Contemporary thinking views medication-assisted treatment (MAT) as the best strategy for pregnant women with an opioid use disorder. This strategy is based on fetal concerns and the historically high risk of relapse with detoxification approaches. Recent data indicate that fetal risk from detoxification to be minimal if any. Guidelines for detoxification do not currently exist. In this proposal we aim to evaluate 3 components of detoxification that may impact the risk of cravings and relapse. We will assess dose reduction quantity, dose reduction frequency and dosing frequency as each may impact the success rate of detoxification. These 3 elements impact the magnitude of perturbations in plasma BUP concentrations (a measure of BUP exposure) that occur with each dose reduction and the rate of accommodation of opioid induced brain changes.

标题：孕期丁丙诺啡治疗的药理学策略 摘要 这项提案将挑战目前几种临床方法，以管理患有 阿片类药物使用障碍。丁丙诺啡(BUP)在妊娠妇女中的剂量是基于对非妊娠妇女的研究 这表明当血浆BUP浓度为-1 ng/ml时，就会出现戒断症状。 孕妇没有这样的数据，但这是确定适当的剂量方案的先决条件 孕妇的BUP。我们将通过监测接受轻微医疗检查的女性来定义他的门槛 直接撤资。临床阿片类药物戒断量表评分和NAS的芬尼根评分是关键 定义何时发生戒断，从而决定母亲和婴儿的治疗。两个评分系统都不是 基于血浆BUP浓度，因此，可能不能反映真正的阿片类药物戒断。这项建议旨在 开发基于生理学的评分系统，以提高诊断的准确性和优化治疗。这个 NAS的风险被认为与母亲或胎儿接触阿片类药物导致大量使用 药物辅助治疗(MAT)计划中的阿片类药物。这一假设是基于几个小的 结果相互矛盾的研究。这种关系将通过母婴头发、胎盘、 脐带和胎粪可作为孕妇和胎儿慢性暴露的预测指标，因为它们不受母婴接触的影响 分娩时的真实性或急性给药。现代思维对药物辅助治疗的看法 (MAT)是患有阿片类药物使用障碍的孕妇的最佳策略。这一策略是基于胎儿 戒毒方法带来的担忧和历史上的高复发风险。最近的数据表明，胎儿 戒毒的风险极小(如果有的话)。目前还没有戒毒指南。在本建议书中 我们的目标是评估可能影响食欲和复发风险的戒毒的三个组成部分。我们会 评估剂量减少量、剂量减少频率和剂量频率，因为每种频率都可能影响 脱毒成功率。这三个因素影响着等离子体BUP中微扰的大小 每次剂量减少时发生的浓度(BUP暴露的衡量标准)以及 阿片类药物调节引起的脑改变。