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Introduction <p>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.</p> Methods <p>An open-label, phase 1 study (NCT05892757) was conducted in 12 healthy, lactating adult women 1–6&#xa0;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&#xa0;h after dosing and during specified intervals through 24&#xa0;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.</p> Results <p>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&#xa0;h after dosing, the cumulative mean&#xa0;(range) amount of atogepant excreted in breast milk over 24&#xa0;h was 0.009&#xa0;mg (0.005–0.016&#xa0;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&#xa0;ng/mL and 57.0&#xa0;ng/mL, respectively, and the corresponding AUC values were 3270&#xa0;ng·h/mL and 238&#xa0;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 (<i>n</i>&#xa0;=&#xa0;1) and dyspepsia (<i>n</i>&#xa0;=&#xa0;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.</p> Conclusion <p>The cumulative mean amount of atogepant recovered in breast milk over 24&#xa0;h following a 60-mg dose was 0.009&#xa0;mg, with a RID of 0.19%.</p> Clinical Trial&#xa0;Registration <p>NCT05892757; <a href="https://clinicaltrials.gov/study/NCT05892757">https://clinicaltrials.gov/study/NCT05892757</a>.</p>

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

  • 期刊论文

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  • 发表日期：

    2025年6月2日

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

摘要

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.