Milk and plasma pharmacokinetics of single‐dose ubrogepant in healthy lactating women

Abstract

Objective

The objectives of this study were to evaluate the safety, plasma and milk pharmacokinetics, excretion in breast milk, and the relative infant dose of ubrogepant following a single oral dose.

Background

Ubrogepant is a calcitonin gene‐related peptide receptor antagonist approved for the acute treatment of migraine in adults. Preclinical findings in rats demonstrated comparable concentrations of ubrogepant in milk versus plasma; however, the quantification of ubrogepant excretion in human breast milk and breastfed infant exposure have not been previously evaluated.

Methods

This open‐label, phase 1 study (NCT05892757) enrolled healthy, lactating adult women from July 11, 2023, to February 22, 2024. Participants were 1–6 months postpartum and received a single dose of ubrogepant 100 mg (2 × 50 mg tablets) orally. Plasma and breast milk samples were collected for up to 24 h after dosing to evaluate pharmacokinetics and ubrogepant concentrations were determined using validated liquid chromatography tandem mass spectrometry assays. Standard pharmacokinetic parameters were calculated from the plasma concentration and breast milk data using non‐compartmental analyses. The milk‐to‐plasma concentration ratio was calculated based on the ratio of the area under the plasma concentration–time curve from time 0 to infinity (AUC_∞) of human milk to the AUC_∞ of plasma. The relative infant dose was calculated as 100 times the quotient of the body weight‐normalized infant dose and the body weight‐normalized maternal dose. Safety and tolerability were assessed via adverse events, vital signs, electrocardiograms, and clinical laboratory measurements.

Results

A total of 12 women were enrolled who each received a single dose of oral ubrogepant 100 mg. The mean milk‐to‐plasma ratio was 0.23, the cumulative amount of ubrogepant excreted in breast milk was <0.02% and the calculated relative infant dose was 0.15%. The maximum observed breast milk concentration and AUC of ubrogepant in breast milk were significantly lower (75% and 78%, respectively) compared to plasma. Only two mild adverse events were reported.

Conclusion

Less than 0.02 mg of a 100 mg dose of ubrogepant was excreted in breast milk over a 24‐h period. The minimal transfer of ubrogepant into breast milk is not considered clinically relevant.

Plain Language Summary

Research on the properties of ubrogepant and findings from animal studies indicate that this drug may pass from mother to child through breastfeeding. In this study, the amount of ubrogepant that passed into human breast milk was tested along with the relative dose an infant might receive through breastfeeding. Over the 24 h after dosing, very little ubrogepant passed into breast milk, and the minimal transfer of ubrogepant into breast milk is not considered clinically relevant.

Abbreviations

AE

adverse event

AUC_ext

area under the concentration–time curve extrapolated from the time of last measurable concentration to infinite time

AUC_t

area under the plasma or breast milk concentration–time curve from time 0 until the last measurable concentration

AUC_∞

area under the plasma or breast milk concentration–time curve from time 0 to infinity

BETA

apparent terminal phase elimination constant

CGRP

calcitonin gene‐related peptide

CI

confidence interval

C_max

maximum observed plasma or breast milk concentration

IRB

Institutional Review Board

LLOQ

lowest limit of quantitation

PK

pharmacokinetics

RID

relative infant dose

T_max

time to maximum observed plasma or breast milk concentration

ULN

upper limit of normal

INTRODUCTION

Migraine is the third most common disease in the world and the second leading cause of disability globally. ¹ Women are three times more likely to experience migraine than men, ² with peak prevalence occurring between the ages of 25–55 years, coinciding with childbearing. ³

A study in pregnant women found that the course of migraine attacks changed during pregnancy, with many women experiencing a reduction in the number of attacks during all three trimesters. ⁴ However, the study also showed that migraine attacks reappeared as soon as within the month after delivery in over half of the women, making migraine a concern among lactating women.

Ubrogepant is a calcitonin gene‐related peptide (CGRP) receptor antagonist approved for the acute treatment of migraine in adults. ⁵ It is generally safe and well tolerated in studies, ⁵ , ⁶ , ⁷ , ⁸ , ⁹ with a portion of patients achieving freedom from pain 2 h after dosing and an absence of the most bothersome migraine symptoms. ¹⁰ , ¹¹ When taken during the migraine prodrome, patients are also approximately twice as likely as those taking placebo to not develop a moderate or severe headache over the subsequent 48 h. ¹²

However, the pharmacokinetics (PK) and safety of ubrogepant and its excretion in human breast milk have not been previously evaluated during lactation. This lack of evidence about potential infant exposure through breastfeeding may prevent postpartum women from treating their migraine attacks as needed with ubrogepant. Preclinical studies of ubrogepant found that it was excreted in the milk of lactating rats, and the milk concentrations in rats appeared to be comparable to those achieved in plasma. ¹³

Here, we report the results of a single‐dose phase 1 study of ubrogepant in healthy, lactating women to establish how much of the drug is excreted in breast milk over 24 h after dosing and the relative infant dose (RID).

METHODS

The primary objective of this preplanned study was to evaluate the safety, plasma and milk PK, excretion in breast milk, and the RID after a single dose of ubrogepant to lactating women.

Study design and ethics

This open‐label, multicenter, phase 1 study (NCT05892757) was conducted in healthy, lactating adult women, 1–6 months postpartum. The study was conducted at three sites from July 11, 2023, to February 22, 2024, in accordance with the International Council for Harmonisation (ICH) E6 guideline for good clinical practice and the principles of the Declaration of Helsinki and United States Food and Drug Administration guidance on lactation studies. ¹⁴ All participants provided written informed consent, and the investigators obtained approval of the study protocol from Institutional Review Boards (IRBs) at ICON sites in Salt Lake City, Utah (Advarra; IRB00000971) and San Antonio, Texas (Advarra; IRB00000971), and Bio‐Kinetic Clinical Applications, LLC in Springfield, Missouri (Biokinetic Clinical Applications IRB; IRB00002771), before study initiation.

A single dose of ubrogepant 100 mg (2 × 50 mg oral tablets) was administered in the morning on Day 1 after an 8‐h fast and ~2 h before breakfast (Figure 1).

FIGURE 1.

Study design. [Colour figure can be viewed at wileyonlinelibrary.com]

Participants were confined to study sites and supervised for ~3 days, with confinement beginning on Day −1 and ending following the collection of the 24‐h blood and breast milk samples and completion of scheduled study procedures on Day 2.

Eligibility criteria

All participants were female, aged 18–45 years (inclusive), 1–6 months postpartum, and currently lactating and breastfeeding their infant ≥50% of the time. However, participants were not allowed to breast feed for 24 h after ubrogepant dosing. Additionally, participants had a body mass index ≥18.0 to ≤40.0 kg/m², had a normal pregnancy with no clinically significant complications, and delivered one (or more) infant who could be bottle fed. Participants consented to use pasteurized donor milk, formula, or previously pumped and stored milk to feed their infants during confinement. All participants of childbearing potential consented to avoid pregnancy using hormonal contraceptives, tubal ligation, intrauterine device, vasectomized partner, or practicing abstinence while taking the study drug and for ≥30 days after the last dose of the study drug.

Key exclusion criteria included a history of clinically significant or uncontrolled medical illness, clinically significant sensitivity or allergy to any medication or food, dietary restrictions, a history of medical conditions that may affect gastrointestinal motility, a history of malignancy (excluding successfully treated non‐metastatic cutaneous squamous cell, basal cell carcinoma, or localized carcinoma in situ of the cervix) or breast cancer, a history of breast surgery or augmentation, clinically significant illness or hospitalization or procedure within the past 30 days prior to the dose of the study drug, a history of drug or alcohol abuse within the last 6 months, and the use of tobacco products within 180 days prior to the dose of the study drug. Additionally, participants must not be taking any over‐the‐counter and/or prescription medications, vitamins, or herbal supplements (with the exception of contraceptives, hormonal replacement therapy, or medications, vitamins, and/or supplements related to parturition, postnatal care, or milk supply), must not have received a drug by injection in the past 30 days or within a period defined by 5 half‐lives (whichever is longer; with the exception of contraceptives, hormonal replacement therapy, or medications, vitamins, and/or supplements related to parturition, postnatal care, or milk supply), have no use of known cytochrome P450 inhibitors or inducers within 1 month prior to study drug administration, and have no use of ubrogepant in the past 30 days.

Drug concentration and safety measures

The PK plasma samples were collected at 0 (pre‐dose), 1, 2, 3, 4, 6, 8, 12, 16, and 24 h after dosing on Day 1. Breast milk samples were collected using electric double breast pumps (Medela, Baar, Zug, Switzerland) in bisphenol A‐free polypropylene 250 mL bottles without preservatives at Hour 0 (pre‐dose) and time intervals from 0–2, 2–4, 4–8, 8–12, 12–16, and 16–24 h post‐dose on Day 1, with each expression collected in a separate 250 mL bottle and kept refrigerated until the end of the interval. To ensure complete milk collection, participants were instructed to pump both breasts at the conclusion of each collection interval and samples from both breasts were combined into a single sample per interval collection. The pooled volume for each interval was determined and recorded. The concentration of ubrogepant in plasma and breast milk was analyzed using validated protein precipitation extraction with liquid chromatography and tandem mass spectrometric methods. ⁷

All PK parameters were estimated using non‐compartmental methods and included the area under the plasma or breast milk concentration–time curve extrapolated from the time of last measurable concentration to infinite time (AUC_ext), the area under the plasma or breast milk concentration–time curve from time 0 to the last measurable concentration (AUC_t), the area under the plasma or breast milk concentration–time curve from time 0 to infinity (AUC_∞), the average plasma concentration, the maximum observed plasma or breast milk concentration (C_max), the time to C_max (T_max), and the terminal phase elimination half‐life. For the breast milk collections, the midpoint of each collection interval was used. C_max and T_max were determined from the observed plasma or breast milk concentration–time data.

The following safety evaluations were performed during the study: adverse event (AE) monitoring, vital sign measurements, electrocardiogram variables, and clinical laboratory testing (hematology, chemistry, and urinalysis). Additionally, the following AEs of special interest were monitored: treatment‐emergent elevated alanine transaminase or aspartate aminotransferase laboratory value ≥3 × upper limit of normal (ULN), elevated alanine transaminase or aspartate aminotransferase laboratory value ≥3 × ULN with an elevated total bilirubin laboratory value ≥2 × ULN and, at the same time, an alkaline phosphatase laboratory value <2 × ULN.

Statistical analysis

Descriptive statistics were generated for demographic variables and for the plasma/milk concentrations at each time point of collection and for each of the PK parameters.

Assuming a coefficient of variation of 25% for AUCs (milk and plasma) of ubrogepant and an intra‐participant correlation of 0.5, a power analysis was conducted while designing the study. Based on this analysis, a sample size of 12 participants completing the trial was selected to provide ≥90% power to show the fold difference of true milk‐to‐plasma ratio, with its point estimate being ≤1.2 (e.g., RID 0.5% vs. 0.6% or AUC ratio 0.2 vs. 0.24) at a significance level of 0.05. The present total sample size provided an ~92% probability of observing an AE with an incidence rate of 10%. The confidence intervals reported were based on two separate one‐sided tests, each conducted at a significance level of 0.05.

The PK parameters of C_max and T_max were determined directly from the plasma/milk concentration–time data. The value of the apparent terminal phase elimination rate constant (BETA) was obtained from the slope of the least squares linear regression of the logarithms of the breast milk concentration versus time data from the terminal log‐phase of the profile. The range of concentration–time points selected for the calculation was identified by the maximum adjusted R² value from the regressions from all possible ranges of data points that began at a data point after T_max but included three or more data points and extended to the last measurable concentration. The AUC_t was calculated using the linear trapezoidal rule, and AUC_ext was calculated by dividing the last measurable breast milk/plasma concentration by BETA. AUC_∞ was calculated as the sum of AUC_t and AUC_ext. The percentage of the contribution of AUC_ext to the overall AUC_∞ was calculated by dividing the AUC_ext by the AUC_∞ and multiplying this quotient by 100. The amount of drug recovered in breast milk from 0 to 24 h was calculated as the sum of the products of each breast milk concentration and collected volume of breast milk over the corresponding collection interval. The percentage of drug recovered in breast milk was calculated as 100 × the amount of drug recovered in breast milk from 0 to 24 h divided by the dose. The milk‐to‐plasma ratio was determined by calculating the ratio of the AUC_∞ of the drug in breast milk to the AUC_∞ of the drug in plasma. The RID was calculated as 100 × the body weight‐normalized infant dose (the product of the milk‐to‐plasma ratio, the average maternal plasma concentration, and standardized milk consumption [150 mL/kg/day]) divided by the body weight‐normalized maternal dose (the quotient of maternal dose [mg/day] and maternal weight [kg] at screening). ¹⁵

A linear mixed effects analysis was performed for the natural logarithms of C_max, AUC_t, and AUC_∞, as the PK parameters are known to follow log‐normal distributions. Mixed model analysis was used to account for the correlations among longitudinal observations within a participant. These analyses were not adjusted for any covariance. The relative bioavailability of ubrogepant in milk relative to that in plasma was assessed by point estimates along with two‐sided 90% confidence intervals obtained from the analyses of the natural logarithms of C_max, AUC_t, and AUC_∞.

Any plasma or breast milk samples below the lowest limit of quantification (LLOQ; 1.00 ng/mL in both matrices) were reported as 0.

There were no missing data, therefore no imputation methods were required. All analyses were performed using the Statistical Analysis System (SAS), version 9.4 (SAS Institute Inc., Cary, NC 27513).

RESULTS

A total of 12 participants were enrolled and completed the study. The mean age was 28.2 years, and 83% were White (Table 1).

TABLE 1.

Baseline demographics of the 12 participants who received a single dose of ubrogepant 100 mg.

Variable	Value
Age, years, mean (SD; range)	28.2 (3.21; 24–34)
Weight, kg, mean (SD; range)	78.8 (19.0; 54.8–111)
Height, cm, mean (SD; range)	164 (6.82; 152–176)
BMI, kg/m2, mean (SD; range)	29.0 (5.86; 21.4–39.8)
Race, n (%)
White	10 (83)
Black	2 (17)

Abbreviations: BMI, body mass index; SD, standard deviation.

Pharmacokinetics

The concentrations of ubrogepant in breast milk were observed to be below the LLOQ at 16–24 h after dosing for 10/12 (83%) participants (Figure 2). The cumulative amount of ubrogepant recovered in breast milk over the 24 h after dosing was 0.014 mg (0.014% of the 100 mg dose). The mean milk‐to‐plasma ratio was 0.23, and the mean RID was 0.15% (Table 2).

FIGURE 2.

Mean (standard deviation) ubrogepant plasma and breast milk concentration–time profiles on (A) linear, (B) log‐linear scale. N, number of participants. Error bars indicate standard deviation. [Colour figure can be viewed at wileyonlinelibrary.com]

TABLE 2.

Plasma and breast milk pharmacokinetic parameters of ubrogepant in the 12 participants who received a single dose of ubrogepant 100 mg.

PK parameter	Plasma	Breast milk
Cmax, ng/mL, mean (SD)	384 (152)	92.8 (30.7)
Tmax, h, median (range)	1.0 (1.0–2.0)	1.0 (1.0–1.0)
AUCt, ng × h/mL, mean (SD)	1390 (423)	299 (78.7)
AUC∞, ng × h/mL, mean (SD)	1400 (423)	306 (80.2)
Drug recovered in breast milk, %, mean (SD)	–	0.014 (0.0051)
Milk‐to‐plasma ratio, a mean (SD)	–	0.23 (0.042)
RID, b %, mean (SD)	–	0.15 (0.056)

Abbreviations: AUC_∞, area under the plasma or breast milk concentration–time curve from time 0 to infinity; AUC_t, area under the plasma or breast milk concentration–time curve from time 0 until the last measurable concentration; C_max, maximum observed plasma or breast milk concentration; PK, pharmacokinetics; RID, relative infant dose; SD, standard deviation; T_max, time to maximum observed plasma or breast milk concentration.

^a Milk‐to‐plasma ratio was calculated as the ratio of the AUC_∞ of human breast milk to the AUC_∞ of human plasma.

^b RID was calculated as (body weight‐normalized infant dose)/(body weight‐normalized maternal dose) × 100.

The C_max and AUC of ubrogepant in breast milk were significantly lower by ~75% and ~78%, respectively, compared with plasma (Table 3).

TABLE 3.

Relative bioavailability and 90% confidence intervals of ubrogepant in breast milk compared to that in plasma.

PK parameter	Central value		Relative bioavailability
	Test (Milk)	Reference (Plasma)	Point estimate	90% CI
Cmax, ng/mL	87.4	351	0.25	0.22–0.28
AUCt, ng × h/mL	289	1321	0.22	0.20–0.24
AUC∞, ng × h/mL	296	1340	0.22	0.20–0.24

Abbreviations: AUC_∞, area under the plasma or breast milk concentration–time curve from time 0 to infinity; AUC_t, area under the plasma or breast milk concentration–time curve from time 0 until the last measurable concentration; CI, confidence interval; C_max, maximum observed plasma or breast milk concentration; PK, pharmacokinetics.

Safety

A single 100 mg dose of ubrogepant was generally well tolerated (Table 4) in these 12 participants. One participant reported a treatment‐emergent AE of nausea that was assessed as having a reasonable possibility of being related to the study drug, and one participant reported an ear infection that was not related to the study drug.

TABLE 4.

Summary of treatment‐emergent adverse events.

Body system, n (%)	Ubrogepant 100 mg (N = 12)
Any adverse event	2 (17)
Gastrointestinal disorders	1 (8)
Nausea	1 (8)
Infections and infestations	1 (8)
Ear infection	1 (8)

Overall, all treatment‐emergent AEs were mild in severity, and no new safety issues were reported. There were no deaths, severe AEs, or AEs of special interest. Additionally, there were no clinically significant changes in vital signs, electrocardiograms, or laboratory measures during the study.

DISCUSSION

In preclinical trials of ubrogepant, oral dosing in lactating rats resulted in levels of ubrogepant in milk comparable to peak plasma concentrations. ¹³ , ¹⁶ The excretion of a drug in human breast milk depends on several factors including lipophilicity, as drugs with higher lipophilicity are more likely to be excreted in breast milk. ¹⁷ , ¹⁸ Lipophilicity is measured by the logarithm of the partition coefficient, or logP. ¹⁹ The logP of ubrogepant is 3.1, ²⁰ similar to other currently approved gepants (atogepant 3.4, rimegepant: 2.3, zavegepant: 3.1). ²¹ , ²² , ²³

This open‐label, phase 1 study of ubrogepant in healthy, lactating adult women found that the exposures (C_max and AUC) of ubrogepant in breast milk were significantly lower by ~75% and ~78%, respectively, compared to systemic exposure. The mean milk‐to‐plasma ratio was 0.23, and the cumulative amount of ubrogepant excreted in breast milk was 0.014 mg, with a calculated RID of 0.15%. A RID of <10% is generally considered safe based on a World Health Organization Working Group report (1996) where 87% of drugs surveyed had a RID of <10%. ²⁴ Thus, a single dose of ubrogepant with a RID of 0.15% suggests minimal risk to breast fed infants. The approved adult dose of ubrogepant is 50–100 mg orally, with a maximum daily dose of 200 mg/day. ¹⁶ Assuming an average female adult weight of 60 kg, this translates to a dose range of approximately 0.8 to 1.7 mg/kg. The average newborn infant weighs ~3.1 kg. ²⁵ Assuming an infant consumes all the milk produced in 24 h after the ubrogepant dosing and receives the total amount (0.014 mg) of drug excreted in breast milk, the daily dose for the infant would be 0.005 mg/kg. This translates to ~340‐fold lower dose compared to adults and is unlikely to elicit significant pharmacological activity in lieu of the “as needed” dosing of ubrogepant to patients with migraine.

In comparison, rimegepant, another small molecule CGRP receptor antagonist approved for the acute treatment of migraine, was found to have a similar milk‐to‐plasma ratio (0.20) but a slightly higher RID (0.51%). ²⁶ Rimegepant concentrations in breast milk samples were reported up to 36 h after single dose administration in lactating women, whereas ubrogepant concentrations in breast milk were below the LLOQ in 10 out of 12 participants after 16 h. Lactation data for zavegepant, the most recent gepant to receive approval for acute use in migraine in the United States, is not yet available.

There were some minor differences in the design of the rimegepant study versus the one presented here. The study of rimegepant included women who were 2 weeks to 6 months postpartum versus our study that included women 1–6 months postpartum, plasma PK samples were collected at 0 (pre‐dose), 1, 2, 4, and 8 h post‐dose versus 0 (pre‐dose), 1, 2, 3, 4, 6, 8, 12, 16, and 24 h post‐dose, and milk PK for 36 h versus 24 h, respectively. Additionally, the study of rimegepant used a population PK model to calculate the plasma PK parameters, whereas our study used a non‐compartmental method.

As CGRP is a potent vasodilator and is expressed in breast tissue, CGRP receptor inhibitors, such as ubrogepant, could reduce the blood flow to breasts, lower milk production, and potentially impact infant growth. In such cases, supplemental feeding may be warranted.

Non‐steroidal anti‐inflammatory drugs and triptans are recommended for the treatment of mild‐to‐moderate and moderate‐to‐severe migraine headaches, respectively, ²⁷ , ²⁸ but not all doses are safe for breastfeeding infants. Acetylsalicylic acid has a RID of 2.5–10.8%, and only low doses (75–162 mg/day) are considered safe while breastfeeding. ²⁹ Diclofenac (RID: 1.4%) and naproxen (RID: 3.3%) are considered moderately safe, ketoprofen (RID: 0.31%) is excreted in low levels but is not preferred due to other potential AEs in infants, and ibuprofen (RID: 0.1–0.7%) is considered the safest choice. ²⁹ There are currently seven approved triptans in the United States, and six have published data on the excretion of drug in human breast milk. No studies have been conducted on frovatriptan due to its long half‐life (26 h). ³⁰ A 2021 study found that the calculated RID levels for the remaining six drugs were <10% of the maternal weight‐adjusted dose (almotriptan 6.5%, eletriptan: 2.0%, naratriptan 9.1%, rizatriptan 5.6%, sumatriptan: 1.8%, and zolmitriptan 3.6%). ³⁰ Compared to all these approved drugs for the acute treatment of migraine, the lower RID of ubrogepant suggests that it could be an option for the acute treatment of migraine in breastfeeding women.

Ubrogepant was generally well tolerated following a single 100 mg dose in 12 participants, with all treatment‐emergent AEs being mild. There were no deaths or serious AEs. Vital signs, clinical laboratory measurements, and electrocardiogram results showed no significant changes throughout the study, and no new safety issues were identified.

The single‐dose design of this study was well suited for ubrogepant given the short half‐life of the drug (5–7 h ⁵ ), which ensures rapid clearance to resume breastfeeding in 24 h, and it's as needed usage, which aligns with the intended intermittent administration. Intensive PK sampling under controlled conditions contributed to quality and reliable data to make meaningful conclusions. However, given that only a single dose of ubrogepant was tested, no definite conclusions can be drawn about the impact of repeated dosing on milk transmission. Given the short elimination half‐life along with the fact that breast milk concentrations of ubrogepant were below the LLOQ in majority of the participants after 16 h, and the dose‐linear PK of ubrogepant, a breast‐fed infant is unlikely to receive a pharmacologically relevant dose of ubrogepant following two doses (2 h apart) to the mother. Additionally, the limited sample size may not have adequately captured inter‐individual variability. Furthermore, due to the strict inclusion and exclusion criteria and the minimal racial variation in the study, these results may not reflect the real‐world usage and be generalizable to a broader population of lactating women. Given the limited sample size in the study and the variability (due to heterogeneity in lactation physiology and drug metabolism, concomitant medications, diet, etc.), a population PK analysis based on sparse PK sampling in a larger patient population to test the effect of all potential variables on ubrogepant milk PK and infant exposure could either confirm the conclusions of the present study or provide more useful information to prescribers.

CONCLUSION

Less than 0.02 mg of a 100 mg single dose of ubrogepant was excreted in breast milk over a 24‐h period. The minimal transfer of ubrogepant into breast milk is not considered clinically relevant.

AUTHOR CONTRIBUTIONS

Ramesh R. Boinpally: Conceptualization; formal analysis; methodology; writing – original draft; writing – review and editing. Jonathan H. Smith: Conceptualization; formal analysis; investigation; writing – review and editing. Eric Cohen: Conceptualization; formal analysis; methodology; writing – review and editing. Joel M. Trugman: Conceptualization; investigation; methodology; writing – review and editing.

CLINICAL TRIALS REGISTRATION NUMBERS

NCT05892757; https://clinicaltrials.gov/study/NCT05892757.

FUNDING INFORMATION

This work was supported by AbbVie. AbbVie participated in the design, study conduct, analysis and interpretation of data, as well as the writing, review, and approval of the publication.

CONFLICT OF INTEREST STATEMENT

Ramesh R. Boinpally, Jonathan H. Smith, and Eric Cohen are employees, and Joel M. Trugman is a former employee of AbbVie and may hold AbbVie stock or options.

Boinpally RR, Smith JH, Cohen E, Trugman JM. Milk and plasma pharmacokinetics of single‐dose ubrogepant in healthy lactating women. Headache. 2025;65:1190‐1197. doi: 10.1111/head.14960