Plasma and breast milk pharmacokinetics of suvorexant in healthy lactating women.

AIM: This paper aims to evaluate the plasma and breast milk pharmacokinetics of suvorexant, an orexin receptor antagonist used to treat insomnia at a maximum dose of 20 mg, in healthy lactating women. METHODS: The paper reports on an open-label Phase 1 study in 12 healthy lactating women. Participants received a single oral dose of 20-mg suvorexant following an overnight fast. Blood and breast milk samples for determination of suvorexant and its hydroxy suvorexant metabolite (M9) pharmacokinetics were collected up to 36 h postdose. Participants were required to discontinue feeding their infants with breast milk from study intervention through 60 h postdose to minimize the risk of exposure of suvorexant to an infant. RESULTS: Following a 20-mg dose, suvorexant exposures in breast milk were markedly lower than plasma exposures (in terms of both area-under-the-plasma concentration-over-time-curve [AUC] and Cmax) as indicated by the breast milk to plasma ratio of 0.077 to 0.080. The mean amount of suvorexant recovered in breast milk by 36 h was 0.011 mg. Approximately 82% of the suvorexant that was excreted in breast milk was excreted by 24 h. The mean estimated theoretical infant daily dose was 0.0016 mg/kg/day, reflecting a relative infant dose of approximately 0.7% of the body weight normalized maternal dose. CONCLUSION: Following a 20-mg dose in healthy lactating women, suvorexant exposure in breast milk was markedly lower than plasma exposure. The mean estimated theoretical infant daily dose was less than 1% of the maternal dose.