Human Milk and Plasma Pharmacokinetics of Single-Dose Rimegepant 75 mg in Healthy Lactating Women

OBJECTIVE: Investigate whether rimegepant—an oral small molecule calcitonin gene-related peptide receptor antagonist for the treatment of migraine—is excreted in human milk after a single 75 mg dose and characterize its concentration–time profile in the plasma and milk of healthy lactating women to determine the relative infant dose (RID). METHODS: This open-label, single-center study enrolled healthy lactating women aged 18–40 years with a gestation of 37–42 weeks and uncomplicated delivery of a single healthy child ≥2 weeks (14 days) and ≤6 months before study drug administration. Plasma samples were collected 0, 1, 2, 4, and 8 hours postdose; human milk samples were collected at 0, 1, 2, 4, 8, 12, 16, 24, 32, and 36 hours. The milk:plasma drug concentration ratio was estimated as the ratio of the human milk:plasma areas under the curve. The RID (%) was calculated as 100 times the quotient of the body weight-normalized infant and maternal doses. RESULTS: Subjects (N = 12) were enrolled between 25 January and 15 September 2020. The mean (standard deviation [SD]) age was 29.8 (3.6) years; mean (SD) body mass index was 26.8 (4.9) kg/m(2). The mean (SD) RID of rimegepant was 0.51% (0.14). The mean (SD) body-weight normalized infant dose was 0.005 (0.001) mg/kg/day, the mean (SD) body-weight normalized maternal dose was 1.04 (0.18) mg/kg/day, and mean (SD) maternal body weight was 74.0 (13.3) kg. CONCLUSION: On a weight-adjusted basis, the mean RID of rimegepant was <1% of the maternal dose.