Prevention of Neonatal Abstinence Syndrome

描述（由申请人提供）：滥用阿片类药物成瘾已成为美国增长最快的药物问题，这对孕妇及其婴儿产生了影响。在加州分娩时母体阿片类药物使用的流行率约为1%。新生儿戒断综合征（NAS）是一组麻醉药品戒断症状，在42%至94%的麻醉药品依赖母亲所生的婴儿中出现。对于这种严重的综合征没有预防性治疗，这可能导致新生儿重症监护室的住院和治疗时间延长。基于遗传学的发现，我们证明了5-HT 3拮抗剂（昂丹司琼）的管理，防止在小鼠和人类的实验研究中的麻醉药物戒断症状。由此，我们假设，在分娩前对使用麻醉剂的孕妇给予昂丹司琼，然后对新生儿给予昂丹司琼3天，可以降低NAS症状的发生率或严重程度。昂丹司琼是一种广泛使用的药物，在孕妇中具有大量的安全性记录，但我们不知道怀孕对昂丹司琼的药代动力学有什么影响，也很难预测出生时的昂丹司琼药代动力学。因此，我们将首先进行详细的昂丹司琼在孕妇和新生儿中的药代动力学特征。除了提供有关妊娠期间和新生儿药物代谢差异的重要信息外，这些结果将确保在随后的疗效研究中选择适当的昂丹司琼剂量用于治疗母亲和新生儿。在本研究的第二部分，我们将进行一项多中心、随机、双盲和安慰剂对照试验，以确定昂丹司琼治疗是否会降低吸毒母亲所生婴儿NAS的发生率（需要麻醉药物治疗的婴儿百分比）或严重程度（所需麻醉药物总量、住院时间、症状严重程度评分）。该项目测试了一种非常新颖的方法，用于预防与麻醉药品滥用有关的一种重要的妊娠并发症。如果对使用麻醉药品的母亲和她们的婴儿短期给予昂丹司琼，可以预防或改善新生儿麻醉药品戒断症状的发展，这将减少人类的痛苦和阿片类药物滥用日益增加的社会成本。

DESCRIPTION (provided by applicant): The misuse of an addiction to opioid medications has become the most rapidly increasing drug problem in the US, which has consequences for pregnant mothers and their babies. The prevalence of maternal opioid drug use at the time of delivery in California is approximately one percent. The neonatal abstinence syndrome (NAS) is a constellation of narcotic drug withdrawal symptoms that develops in 42 to 94 percent of infants born to narcotic dependent mothers. There are no preventative treatments for this severe syndrome, which can result in a prolonged hospitalization and treatment in a neonatal intensive care unit. Based upon a genetic discovery, we demonstrated that administration of a 5-HT3 antagonist (ondansetron) prevented the symptoms of narcotic drug withdrawal in experimental studies in mice and in humans. From this, we hypothesize that ondansetron administration to pregnant narcotic-using mothers just prior to delivery, followed by a 3-day period of ondansetron administration to the neonate, could reduce the incidence or severity of NAS symptoms. Ondansetron is a broadly utilized drug with a substantial safety record in pregnant women, but we do not know what effect pregnancy may have on ondansetron pharmacokinetics and it is hard to predict ondansetron pharmacokinetics at birth. Therefore, we will first perform a detailed characterization of ondansetron pharmacokinetics in pregnant mothers and in neonates. Besides providing important information about differences in drug metabolism during pregnancy and in neonates, these results will ensure that appropriate ondansetron doses are selected for treatment of the mothers and neonates in the subsequent efficacy study. In the second part of this study, we will conduct a multi-center, randomized, double blind, and placebo-controlled trial to determine whether ondansetron treatment will reduce the incidence (percentage of infants requiring narcotic drug treatment) or severity (total amount of narcotic drug required, length of hospitalization, symptom severity scores) of NAS in babies born to narcotic-using mothers. This project tests a very novel approach for preventing an important pregnancy-related complication of narcotic drug abuse. If a brief period of ondansetron administration to the mothers that use narcotic drugs, and to their babies, can prevent or ameliorate the development of narcotic drug withdrawal symptoms in neonates, this would reduce human suffering and the growing societal cost of opiate abuse.