Safety, Efficacy, Pharmacokinetics, and Pharmacogenomics of Extended-Release Naltrexone in Pregnant Women - Administrative Supplement

缓释纳曲酮在孕妇中的安全性、功效、药代动力学和药物基因组学 - 行政补充文件

• 批准号: 10620577
• 负责人: Elisha Wachman
• 金额: $ 12.05万
• 依托单位: BOSTON MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10620577
• 关键词: Administrative Supplement; Adverse event; Age-Months; Agonist; Animals; Biological Assay; Blood; Boston; Breast Feeding; Buprenorphine; California; Caring; Clinic; Cohort Studies; Collection; DNA Methylation; Data; Development; Dose; Drug Kinetics; Enrollment; Epigenetic Process; Exposure to; FDA approved; Formulation; Future; Genetic Polymorphism; Goals; Growth; Human Milk; Individual; Infant; Infant Health; Infrastructure; Injectable; Injections; Kinetics; Knowledge; Laboratories; Lactation; Maternal Health; Measurement; Measures; Medical center; Methadone; Modification; Mothers; Mucous Membrane; Naltrexone; Neonatal Abstinence Syndrome; Opioid; Opioid Antagonist; Outcome; Overdose; Parents; Perinatal; Persons; Pharmaceutical Preparations; Pharmacogenomics; Plasma; Postpartum Period; Postpartum Women; Pregnancy; Pregnancy Outcome; Pregnant Women; Prospective Studies; Provider; Pyrrolidinones; Recovery; Risk; Safety; Sampling; Time; Toxic effect; Umbilical Cord Blood; Universities; Urine; Woman; absorption; base; clinical practice; cohort; comparative; experience; fetal; high risk; human data; improved; individualized medicine; infant outcome; maternal outcome; neonatal outcome; neurodevelopment; opioid epidemic; opioid use disorder; pregnant; prenatal exposure; prospective; routine care; side effect; standard of care; subcutaneous; success; treatment response

PROJECT ABSTRACT The current US opioid epidemic includes a rising number of pregnant and postpartum women struggling with opioid use disorders (OUD). The standard of care for pregnant and postpartum women with OUD is treatment with medication for OUD (MOUD), specifically methadone or sublingual buprenorphine (SL BUP). However, in recent years, newer options for the treatment of OUD have emerged that have not been studied in pregnant and postpartum women. Specifically, the use of naltrexone (NTX), an opioid antagonist, could be advantageous in pregnant women with OUD as it avoids fetal exposure to opioids and eliminates the risk for neonatal opioid withdrawal syndrome (NOWS). Preliminary studies demonstrate minimal impact on pregnancy and fetal outcomes with NTX exposure, however there is an overall lack of prospective human data fully evaluating safety, efficacy, and the full range of outcomes. In addition, the pharmacokinetics, pharmacogenomics, breast milk transfer and safety of NTX when used during pregnancy and the postpartum period are unknown. Our parent study examined 50 pregnant women on NTX compared with 50 on SL BUP in a multi-centered prospective comparative cohort study with the following 4 specific aims: 1) Safety and efficacy of NTX versus SL BUP: Mother-infant dyads are followed throughout the pregnancy until 12 months postpartum to examine maternal outcomes, fetal outcomes, and infant outcomes. 2) Pharmacokinetics of NTX: The pharmacokinetics of NTX in pregnant and postpartum women is examined. 3) Pharmacogenomics and epigenetic modification: We examine the impact of genetic polymorphisms on treatment response, and the impact of maternal treatment on DNA methylation. 4) NTX breastfeeding safety. We will measure breast milk concentrations from lactating women on NTX along with simultaneous maternal and infant plasma concentrations. Recently, extended-release formulations of subcutaneous buprenorphine (SC BUP) have been developed and are commonly used in non- pregnant individuals. These long-acting formulations of BUP allow for more individualization of treatment and could improve compliance and treatment retention. In clinical practice, more providers have moved towards using SC BUP in the postpartum period, however no studies of SC BUP in pregnant, postpartum, or lactating women have been conducted. We have added the following two aims as part of an administrative supplement: 1) Pharmacokinetics of SC BUP in lactating women and their infants: We will enroll 10 postpartum women who are on SC BUP who are breastfeeding to determine pharmacokinetics and breastmilk levels. 2) Safety and efficacy of SC BUP in postpartum breastfeeding women and their infants: We will follow the dyads to 12 months postpartum to examine maternal and infant outcomes. The results of this study hold the promise to guide planned future studies examining the use of both NTX and other agonist medications in the context of best practice treatment for OUD in pregnancy and postpartum period in order to improve long-term maternal and infant outcomes.

项目摘要 当前美国阿片类药物流行病包括越来越多的孕妇和产后妇女与阿片类药物作斗争 阿片类药物使用障碍 (OUD)。患有 OUD 的孕妇和产后妇女的护理标准是治疗 使用 OUD (MOUD) 药物，特别是美沙酮或舌下含服丁丙诺啡 (SL BUP)。然而，在 近年来，出现了治疗 OUD 的新选择，但尚未在孕妇和孕妇中进行过研究。 产后妇女。具体来说，使用纳曲酮（NTX）（一种阿片类拮抗剂）可能有利于 使用 OUD 的孕妇，因为它可以避免胎儿接触阿片类药物并消除新生儿阿片类药物的风险 戒断综合症（NOWS）。初步研究表明对妊娠和胎儿的影响极小 NTX 暴露的结果，但是总体上缺乏充分评估安全性的前瞻性人类数据， 功效和全方位的结果。此外，药代动力学、药物基因组学、母乳 NTX 在怀孕期间和产后使用时的转移和安全性尚不清楚。我们的家长 在一项多中心前瞻性研究中，对 50 名服用 NTX 的孕妇与 50 名服用 SL BUP 的孕妇进行了比较 比较队列研究具有以下 4 个具体目标： 1) NTX 与 SL BUP 的安全性和有效性： 母婴二元组在整个怀孕期间直至产后 12 个月进行跟踪，以检查母体 结局、胎儿结局和婴儿结局。 2) NTX的药代动力学：NTX在体内的药代动力学 孕妇和产后妇女接受检查。 3）药物基因组学和表观遗传修饰：我们检查 遗传多态性对治疗反应的影响，以及母亲治疗对 DNA 的影响 甲基化。 4) NTX母乳喂养安全。我们将测量哺乳期妇女的母乳浓度 NTX 以及同时母亲和婴儿的血浆浓度。最近，延长发布 皮下注射丁丙诺啡 (SC BUP) 制剂已开发出来，通常用于非 怀孕的个体。这些 BUP 长效制剂可实现更加个体化的治疗和 可以提高依从性和治疗保留率。在临床实践中，更多的提供者已经转向使用 SC BUP 在产后期间使用，但尚无针对孕妇、产后或哺乳期妇女的 SC BUP 研究 已进行。我们添加了以下两个目标作为行政补充的一部分：1) SC BUP 在哺乳期妇女及其婴儿中的药代动力学：我们将招募 10 名产后妇女，她们是 母乳喂养的 SC BUP 以确定药代动力学和母乳水平。 2）安全性和有效性 SC BUP 在产后母乳喂养妇女及其婴儿中的应用：我们将跟踪两组至 12 个月 产后检查母婴结局。这项研究的结果有望指导计划 未来的研究将在最佳实践的背景下检验 NTX 和其他激动剂药物的使用 妊娠期和产后期的OUD治疗，以改善母婴长期健康状况 结果。

项目成果

National Provider Survey: Use of Naltrexone for Pregnant Individuals with Substance Use Disorders.

全国提供者调查：纳曲酮对患有药物使用障碍的孕妇的使用。

• 发表时间: 2023-11-01
• 作者: Deflorimonte, Chloe;Glissendorf, Viktorria;Hofer, Julia;Cai, Annette;Iannella, Nicole;Boateng, Jeffery O;Carter, Ginny;Saia, Kelley A;Jones, Hendree E;Wachman, Elisha M
• 通讯作者: Wachman, Elisha M

Pilot Study Comparing Adverse Cardiorespiratory Events among Pharmacologically and Nonpharmacologically Treated Infants Undergoing Monitoring for Neonatal Abstinence Syndrome.

比较接受新生儿戒断综合症监测的药物和非药物治疗婴儿的不良心肺事件的初步研究。

• 发表时间: 2020
• 作者: Davala, Spoorthi;Hansbury, Aaron;Miller, Melissa;Boateng, Jeffery;Shrestha, Hira;Wachman, Elisha M
• 通讯作者: Wachman, Elisha M

Academy of Breastfeeding Medicine Clinical Protocol #21: Breastfeeding in the Setting of Substance Use and Substance Use Disorder (Revised 2023).

母乳喂养医学会临床方案

• 发表时间: 2023-10
• 作者: Harris, Miriam;Schiff, Davida M;Saia, Kelley;Muftu, Serra;Standish, Katherine R;Wachman, Elisha M
• 通讯作者: Wachman, Elisha M

Advances in the Care of Infants With Prenatal Opioid Exposure and Neonatal Opioid Withdrawal Syndrome.

产前阿片类药物暴露和新生儿阿片类药物戒断综合征婴儿的护理进展。

• 发表时间: 2024-01-01
• 影响因子: 8
• 作者: Mascarenhas, Margarida;Wachman, Elisha M;Chandra, Iyra;Xue, Rachel;Sarathy, Leela;Schiff, Davida M
• 通讯作者: Schiff, Davida M

Naltrexone Treatment for Pregnant Women With Opioid Use Disorder Compared With Matched Buprenorphine Control Subjects.

与匹配的丁丙诺啡对照受试者相比，纳曲酮治疗患有阿片类药物使用障碍的孕妇。

• 发表时间: 2019-09
• 影响因子: 3.2
• 作者: Wachman, Elisha M;Saia, Kelley;Miller, Melissa;Valle, Eduardo;Shrestha, Hira;Carter, Ginny;Werler, Martha;Jones, Hendree
• 通讯作者: Jones, Hendree