Pharmacologically-based Strategies for Buprenorphine Treatment During Pregnancy

标题：妊娠期间丁丙诺啡治疗的药理学策略 摘要 这项提议将挑战目前管理孕妇的几种临床方法， 阿片类药物使用障碍妊娠女性中丁丙诺啡（BUP）的剂量基于非妊娠女性中的研究。 提示当血浆BUP浓度<1 ng/ml时出现戒断症状。 对于妊娠女性不存在此类数据，但这是确定适当的给药方案的先决条件。 孕妇中的BUP。我们将通过监测接受轻度医学检查的女性来确定他的阈值， 直接撤退。临床阿片类药物戒断量表评分和NAS的Finnegan评分是 定义何时发生戒断，从而决定母亲和婴儿的治疗。这两种评分系统都不是 基于血浆BUP浓度，因此可能不反映真实的阿片类戒断。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并优化治疗。的 NAS的风险被认为与母体或胎儿暴露于阿片类药物无关，导致大量使用阿片类药物。 药物辅助治疗（MAT）计划中的阿片类药物。这个假设是基于一些小的 结果相互矛盾的研究。这种关系将通过母亲和婴儿的头发，胎盘， 脐带和胎粪作为母体和胎儿慢性暴露的预测因子，因为这些不受母体 真实性或交付时的急性剂量。当代思维观药物辅助治疗 (MAT)作为患有阿片类药物使用障碍的孕妇的最佳策略。该策略基于胎儿 人们的担忧以及戒毒方法复发的历史高风险。最近的数据表明，胎儿 解毒的风险是最小的。目前还没有解毒指南。本提案中 我们的目标是评估解毒的3个组成部分，可能会影响渴望和复发的风险。我们将 评估剂量减少量、剂量减少频率和给药频率，因为每一项都可能影响 戒毒成功率。这3个元素影响等离子体BUP中的扰动幅度 浓度（BUP暴露量的测量），每次剂量降低时发生的浓度和 阿片类药物引起的大脑变化的适应性。

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.