Human Milk and Plasma Pharmacokinetics of Single-Dose Rimegepant 75 mg in Healthy Lactating Women
Teresa E. Baker, Robert Croop, Lisa Kamen, Patty Price, David A. Stock, Andrea Ivans, Rajinder Bhardwaj, Matt S. Anderson, Jennifer Madonia, Joseph Stringfellow, Richard Bertz, Vladimir Coric, Thomas W. Hale
Abstract
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.