OBJECTIVE. In utero exposure to drugs of abuse can lead to neonatal abstinence syndrome, a condition that is associated with prolonged hospitalization. Buprenorphine is a partial μ-opioid agonist used for treatment of adult detoxification and maintenance but has never been administered to neonates with opioid abstinence syndrome. The primary objective of this study was to demonstrate the feasibility and, to the extent possible in this size of study, the safety of sublingual buprenorphine in the treatment of neonatal abstinence syndrome. Secondary goals were to evaluate efficacy relative to standard therapy and to characterize buprenorphine pharmacokinetics when sublingually administered.METHODS. We conducted a randomized, open-label, active-control study of sublingual buprenorphine for the treatment of opiate withdrawal. Thirteen term infants were allocated to receive sublingual buprenorphine 13.2 to 39.0 μg/kg per day administered in 3 divided doses and 13 to receive standard-of-care oral neonatal opium solution. Dose decisions were made by using a modified Finnegan scoring system.RESULTS. Sublingual buprenorphine was largely effective in controlling neonatal abstinence syndrome. Greater than 98% of plasma concentrations ranged from undetectable to ～0.60 ng/mL, which is less than needed to control abstinence symptoms in adults. The ratio of buprenorphine to norbuprenorphine was larger than that seen in adults, suggesting a relative impairment of N -dealkylation. Three infants who received buprenorphine and 1 infant who received standard of care reached protocol-specified maximum doses and required adjuvant therapy with phenobarbital. The mean length of treatment for those in the neonatal-opium-solution group was 32 compared with 22 days for the buprenorphine group. The mean length of stay for the neonatal-opium-solution group was 38 days compared with 27 days for those in the buprenorphine group. Treatment with buprenorphine was well tolerated.CONCLUSIONS. Buprenorphine administered via the sublingual route is feasible and apparently safe and may represent a novel treatment for neonatal abstinence syndrome.
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机译：目的。在子宫内接触滥用药物会导致新生儿戒断综合症，这种情况与长期住院有关。丁丙诺啡是一种局部μ阿片类激动剂，用于治疗成人排毒和维持生命，但从未向患有阿片类戒断综合症的新生儿服用。这项研究的主要目的是证明在这种规模的研究中，舌下丁丙诺啡在治疗新生儿戒断综合症中的可行性以及在尽可能大的程度上的安全性。次要目标是评估相对于标准疗法的疗效，以及舌下给药时丁丙诺啡的药代动力学特征。我们进行了舌下丁丙诺啡治疗鸦片停药的随机，开放标签，主动控制研究。十三名足月婴儿被分配为每天接受舌下丁丙诺啡13.2至39.0μg/ kg的治疗，分3剂每天服用，13例接受护理标准的口服新生儿鸦片溶液。通过使用改良的Finnegan评分系统来确定剂量。结果。舌下丁丙诺啡在控制新生儿禁欲综合症方面非常有效。大于98％的血浆浓度范围从无法检测到〜0.60 ng / mL，低于控制成人禁欲症状所需的浓度。丁丙诺啡与去甲丁丙诺啡的比例大于成年人，表明N-脱烷基化相对受损。 3名接受丁丙诺啡的婴儿和1名接受护理标准的婴儿达到了协议规定的最大剂量，并需要苯巴比妥辅助治疗。新生儿鸦片溶液组的平均治疗时间为32天，丁丙诺啡组为22天。新生儿鸦片溶液组的平均住院时间为38天，而丁丙诺啡组为27天。丁丙诺啡的治疗耐受性良好。通过舌下途径给予丁丙诺啡是可行的，而且显然是安全的，并且可能代表了一种针对新生儿戒断综合征的新疗法。
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