Zuranolone Concentrations in the Breast Milk of Healthy, Lactating Individuals: Results From a Phase 1 Open-Label Study.

ABSTRACT

PURPOSE/BACKGROUND: Zuranolone is a positive allosteric modulator of both synaptic and extrasynaptic γ-aminobutyric acid type A receptors and a neuroactive steroid approved as an oral, once-daily, 14-day treatment course for adults with postpartum depression in the United States. This study assessed zuranolone transfer into breast milk. METHODS/PROCEDURES Healthy, nonpregnant, lactating adult female participants received once-daily 30 mg zuranolone from day (D)1 through D5 in this phase 1 open-label study. The relative infant dose (RID; weight-adjusted proportion of the maternal dose in breast milk over 24 hours) for 30 mg zuranolone was assessed at D5. An RID for 50 mg zuranolone was estimated using a simulation approach across a range of infant ages and weights. FINDINGS/RESULTS: Of 15 enrolled participants (mean age, 30.1 years), 14 completed the study. The mean RID for 30 mg zuranolone at D5 was 0.357%; the mean steady-state milk volume over D3 to D5 decreased from baseline by 8.3%. Overall unbound zuranolone in plasma was low (≤0.49%). Plasma concentrations peaked at D5 before decreasing in a biexponential manner. There was strong concordance between the temporal profiles of zuranolone concentrations in plasma and breast milk. The estimated mean RID for 50 mg zuranolone based on a milk intake of 200 mL/kg per day was 0.984%. All treatment-emergent adverse events reported by participants were mild, the most common being dizziness (n = 3). IMPLICATIONS/CONCLUSIONS: Zuranolone transfer into the breast milk of healthy, nonpregnant, lactating adult female participants was low; the estimated RID for 50 mg zuranolone was <1%, well below the <10% threshold generally considered compatible with breastfeeding.