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 目前，美国阿片类药物流行病包括越来越多的孕妇和产后妇女挣扎在 阿片类药物使用障碍（OUD）。标准的护理孕妇和产后妇女与OUD是治疗 OUD（MOUD）药物，特别是美沙酮或舌下丁丙诺啡（SL BUP）。但在 近年来，出现了治疗OUD的新选择，这些选择尚未在妊娠和 产后妇女。具体而言，使用阿片类拮抗剂纳洛酮（NTX）可能有利于 OUD孕妇，因为它避免了胎儿暴露于阿片类药物，并消除了新生儿阿片类药物的风险 戒断综合征（NOWS）。初步研究表明对妊娠和胎儿的影响最小 NTX暴露的结果，但是总体上缺乏充分评价安全性的前瞻性人体数据， 有效性和全面的结果。此外，药代动力学、药物基因组学、母乳 NTX在妊娠和产后期间使用的转移和安全性尚不清楚。子公司 一项多中心前瞻性研究对50名接受NTX治疗的孕妇和50名接受SL BUP治疗的孕妇进行了比较 比较队列研究，具有以下4个特定目的：1）NTX与SL BUP的安全性和疗效： 在整个怀孕期间，直到产后12个月，对母婴配对进行跟踪， 结果、胎儿结果和婴儿结果。2)NTX的药代动力学： 对孕妇和产后妇女进行检查。3)药物基因组学和表观遗传修饰：我们研究 遗传多态性对治疗反应的影响，以及母体治疗对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沿着母亲和婴儿同时血浆浓度。最近， 已经开发了皮下丁丙诺啡（SC BUP）的制剂，并且通常用于非药物治疗。 怀孕的人。BUP的这些长效制剂允许更个性化的治疗， 可以提高依从性和治疗保留率。在临床实践中，更多的供应商已经转向使用 产后SC BUP，但未在妊娠、产后或哺乳期女性中进行SC BUP研究 已经进行了。作为行政补充的一部分，我们增加了以下两个目标：1） SC BUP在哺乳期女性及其婴儿中的药代动力学：我们将招募10名产后女性， 对母乳喂养的SC BUP进行研究，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作用：我们将随访至12个月 产后检查产妇和婴儿的结果。这项研究的结果有望指导计划 在最佳实践的背景下，进一步研究NTX和其他激动剂药物的使用 妊娠期和产后治疗OUD，以改善长期母婴 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。

• DOI: 10.1097/adm.0000000000001225
• 发表时间: 2023
• 期刊: Journal of addiction medicine
• 影响因子: 5.5
• 作者: Deflorimonte,Chloe;Glissendorf,Viktorria;Hofer,Julia;Cai,Annette;Iannella,Nicole;Boateng,JefferyO;Carter,Ginny;Saia,KelleyA;Jones,HendreeE;Wachman,ElishaM
• 通讯作者: Wachman,ElishaM

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

• DOI: 10.1016/j.ympdx.2020.100027
• 发表时间: 2020-01-01
• 期刊: The journal of pediatrics: X
• 作者: Davala, Spoorthi;Hansbury, Aaron;Wachman, Elisha M
• 通讯作者: Wachman, Elisha M

Hair Cortisol Concentrations in Opioid-Exposed versus Nonexposed Mother-Infant Dyads.

暴露于阿片类药物与未暴露于阿片类药物的母婴二人组的头发皮质醇浓度。

• DOI: 10.1055/s-0043-1778008
• 发表时间: 2023
• 期刊: American journal of perinatology
• 影响因子: 2
• 作者: Morrison,TierneyM;Schiff,DavidaM;Olson,Abigael;Hunter,RichardG;Agarwal,Joel;Work,ErinC;Muftu,Serra;Shrestha,Hira;Boateng,Jeffery;Werler,MarthaM;Carter,Ginny;Jones,HendreeE;Wachman,ElishaM
• 通讯作者: Wachman,ElishaM