Eisai Inc., Nutley, New Jersey, USA.
PPD-Thermo Fisher Scientific, Las Vegas, Nevada, USA.
Br J Clin Pharmacol. 2024 Jan;90(1):158-163. doi: 10.1111/bcp.15880. Epub 2023 Aug 23.
The aim of this study is to determine the cumulative amount of lemborexant (a competitive dual orexin receptor antagonist approved to treat adults with insomnia) excreted in human breast milk and the relative infant dose (RID) as a proportion of daily maternal dose.
E2006-A001-010 was a single-centre, open-label study that enrolled lactating women (≥18 years) who breastfed for ≥5 weeks postpartum. After overnight fasting, subjects received a single 10-mg oral dose of lemborexant. Using a standardized electric pump, milk was sampled before and ≤240 h (10 days) after dosing; combined and total volume were recorded. The cumulative total amount of lemborexant excreted, fraction of dose excreted, daily infant dose and RID were calculated. Lemborexant concentration in human milk was assessed by liquid chromatography with tandem mass spectrometry.
Eight subjects completed the study. The mean cumulative total amount of lemborexant reached 0.0174 mg (coefficient of variation [CV] 54.5%; 0.174% of lemborexant 10 mg administered) in breast milk at 240 h (10 days); ~70% of excreted lemborexant accumulated in the first 24 h. For an infant weighing 6 kg, the daily infant dose was 0.00290 mg kg (CV 54.5%) and the RID was 1.96% (CV 63.1%) of daily maternal dose. Mild treatment-emergent adverse events were reported in 4 subjects; these all resolved by end of study.
Trace quantities of lemborexant were found in human breast milk. Lemborexant was well tolerated by healthy lactating women.
本研究旨在确定在人乳中排泄的雷美替胺（一种已获批用于治疗失眠成人的竞争性双重食欲素受体拮抗剂）的累积量以及作为每日母体剂量的相对婴儿剂量（RID）。
E2006-A001-010 是一项单中心、开放标签研究，招募了至少产后 5 周进行母乳喂养的哺乳期妇女（≥18 岁）。在过夜禁食后，受试者单次口服 10 毫克雷美替胺。使用标准化电动泵，在给药前和≤240 小时（10 天）后采集乳汁样本；合并并记录总体积。计算雷美替胺的累积排泄总量、排泄剂量分数、每日婴儿剂量和 RID。通过液质联用色谱法评估人乳中雷美替胺的浓度。
8 名受试者完成了研究。在 240 小时（10 天）时，人乳中雷美替胺的累积排泄总量达到 0.0174 毫克（变异系数 [CV] 54.5%；雷美替胺 10 毫克给药量的 0.174%）；约 70%的排泄雷美替胺在前 24 小时内积累。对于体重为 6 公斤的婴儿，每日婴儿剂量为 0.00290 毫克/公斤（CV 54.5%），RID 为每日母体剂量的 1.96%（CV 63.1%）。4 名受试者报告了轻微的治疗后不良事件；这些不良事件均在研究结束时得到解决。
在人乳中发现了微量的雷美替胺。雷美替胺在健康的哺乳期妇女中耐受良好。
