Buprenorphine Treatment of Neonatal Abstinence Syndrome

描述（由申请人提供）：55-94%的阿片类药物依赖母亲所生的婴儿被诊断为新生儿戒断综合征（NAS）（美国儿科学会药物委员会，1998年），美国每年约有7000名高危婴儿出生（国家妊娠和健康调查，1996年）。据估计，有2.8%的孕妇使用非法药物，如果从国际上考虑，这个问题当然更大。原本健康的治疗婴儿的住院时间延长，从几周到两个月不等，这对父母和婴儿都是一种负担，并产生很大的经济影响。有必要改进治疗方案。简单地说，从新生儿NAS的角度来看，目标包括安全降低其发病率、严重程度和持续时间，从而减少住院时间（同时与父母分离）和其他药物的暴露。由于丁丙诺啡具有部分mu阿片受体激动剂活性、高受体亲和力和低内在阿片活性，其药理特征与最广泛用于母亲治疗的美沙酮以及最广泛用于NAS的药物之一吗啡有很大不同。使用丁丙诺啡治疗阿片类药物滥用的孕妇的经验表明，丁丙诺啡对胎儿是安全的，并且这些婴儿的NAS可能比子宫内暴露于美沙酮的婴儿的NAS更严重。相对于吗啡，丁丙诺啡治疗NAS应该是安全的，并且可能缩短治疗婴儿的住院时间。这是一项R21申请，用于建立丁丙诺啡舌下治疗NAS的参数，并确定其安全性（IND #68403）。

DESCRIPTION (provided by applicant): Neonatal abstinence syndrome (NAS) is diagnosed in 55-94% or infants born to opioid-dependent mothers (American Academy of Pediatrics Committee on Drugs, 1998), and approximately 7000 at-risk infants are born in the United States each year (National Pregnancy and Health Survey, 1996). It is estimated that 2.8% of pregnant women use illicit drugs, and the problem is of course even larger when considered internationally. Hospitalization time for otherwise-healthy treated infants is prolonged, lasting from several weeks up to two months, which is a burden on both the parent and infant, and has a large financial impact. There is a need for improved treatment options. Simplistically, from the neonatal aspect of NAS, goals would include to safely decrease its incidence, severity, and duration, and thereby decrease the hospitalization time (and simultaneous separation from the parents) and exposure to other medications. Due to its partial mu opioid receptor agonist activity, high receptor affinity, and low intrinsic opioid activity, the pharmacological profile of buprenorphine greatly differs from that of methadone, the most widely used treatment for the mothers, and from that of morphine, one of the most widely used medical treatments for NAS. Experience with treatment of opioid-abusing, pregnant women with buprenorphine indicates that it is safe for the fetus, and that NAS in these infants may be less severe than is seen in infants exposed to methadone in utero. Treatment of NAS with buprenorphine, relative to morphine, should be safe and may result in shorter hospital stays for treated infants. This is an R21 application to establish treatment parameters for NAS with sublingual buprenorphine, and to establish its safety (IND #68403).