阿托格潘在健康哺乳期女性受试者中的药代动力学：一项1期哺乳期研究的结果。

Pharmacokinetics of Atogepant in Healthy Lactating Female Participants: Results from a Phase 1 Lactation Study.

作者信息

Boinpally Ramesh R, Smith Jonathan H, De Abreu Ferreira Rosa L, Trugman Joel M

机构信息

Clinical Pharmacology, AbbVie Inc., Dept. R4PD, AP31-3, 1 North Waukegan Road, North Chicago, IL, 60064, USA.

Clinical Development, AbbVie Inc., North Chicago, IL, USA.

出版信息

Neurol Ther. 2025 Jun 2. doi: 10.1007/s40120-025-00772-4.

DOI:10.1007/s40120-025-00772-4

PMID:40455369

Abstract

INTRODUCTION

Atogepant is approved for the preventive treatment of migraine and is taken orally once daily. This work aimed to characterize the plasma and milk pharmacokinetics of atogepant in lactating females.

METHODS

An open-label, phase 1 study (NCT05892757) was conducted in 12 healthy, lactating adult women 1-6 months postpartum from July 11, 2023, to February 22, 2024. A single 60-mg dose of atogepant was administered to participants to determine atogepant's plasma and milk pharmacokinetics, the excretion of atogepant in breast milk, and the relative infant dose (RID). Atogepant was analyzed using validated LC-MS/MS assays in plasma and breast milk samples collected up to 24 h after dosing and during specified intervals through 24 h, respectively. Plasma and milk pharmacokinetic parameters were estimated using non-compartmental methods and compared using linear mixed-effects models. Safety was assessed via adverse event reporting, clinical labs, vital signs, and ECGs throughout the study.

RESULTS

The mean (range) milk-to-plasma ratio for atogepant was 0.076 (0.023-0.104). With nearly undetectable levels of atogepant in breast milk 16-24 h after dosing, the cumulative mean (range) amount of atogepant excreted in breast milk over 24 h was 0.009 mg (0.005-0.016 mg; 0.015% of 60-mg dose), and the mean (range) RID was 0.19% (0.06-0.33%). The mean plasma and milk peak concentrations of atogepant were 779 ng/mL and 57.0 ng/mL, respectively, and the corresponding AUC values were 3270 ng·h/mL and 238 ng·h/mL, respectively. Atogepant exposures in breast milk were 93% lower compared to plasma. Two participants (16.7%) experienced AEs. These included abdominal pain (n = 1) and dyspepsia (n = 1), both of which were non-serious and mild in severity. No new safety signals were identified in this small group of healthy lactating women.

CONCLUSION

The cumulative mean amount of atogepant recovered in breast milk over 24 h following a 60-mg dose was 0.009 mg, with a RID of 0.19%. CLINICAL TRIAL REGISTRATION: NCT05892757; https://clinicaltrials.gov/study/NCT05892757 .

摘要

简介

阿托格潘已被批准用于偏头痛的预防性治疗，且每日口服一次。本研究旨在描述哺乳期女性体内阿托格潘的血浆和乳汁药代动力学特征。

方法

于2023年7月11日至2024年2月22日，对12名产后1至6个月的健康哺乳期成年女性开展了一项开放标签的1期研究（NCT05892757）。给参与者单次服用60毫克剂量的阿托格潘，以确定阿托格潘的血浆和乳汁药代动力学、其在母乳中的排泄情况以及相对婴儿剂量（RID）。使用经过验证的液相色谱 - 串联质谱法（LC-MS/MS）分别对给药后24小时内及之后特定时间间隔内采集的血浆和母乳样本中的阿托格潘进行分析。使用非房室模型方法估算血浆和乳汁药代动力学参数，并使用线性混合效应模型进行比较。在整个研究过程中，通过不良事件报告、临床实验室检查、生命体征和心电图评估安全性。

结果

阿托格潘的平均（范围）乳汁与血浆比值为0.076（0.023 - 0.104）。给药后16至24小时母乳中阿托格潘水平几乎无法检测到，24小时内母乳中阿托格潘的累积平均（范围）排泄量为0.009毫克（0.005 - 0.016毫克；占60毫克剂量的0.015%），平均（范围）RID为0.19%（0.06 - 0.33%）。阿托格潘的平均血浆和乳汁峰浓度分别为779纳克/毫升和57.0纳克/毫升，相应的AUC值分别为3270纳克·小时/毫升和238纳克·小时/毫升。母乳中阿托格潘的暴露量比血浆低93%。两名参与者（16.7%）出现不良事件。这些不良事件包括腹痛（n = 1）和消化不良（n = 1），均不严重且程度较轻。在这一小群健康哺乳期女性中未发现新的安全信号。