Rapid Disappearance of Zaleplon from Breast Milk after Oral Administration to Lactating Women

Five lactating mothers were administered the therapeutic dose of zaleplon (10 mg) orally in an open‐label, single‐dose, pharmacokinetic study. Plasma and breast milk were sampled through 8 hours after dose administration for subsequent determinations of zaleplon and its major, though inactive, plasma metabolite 5‐oxo‐zaleplon. Zaleplon concentrations peaked in plasma and milk approximately 1 hour after dosing and then disappeared rapidly. The mean terminal half‐life was slightly greater than 1 hour. Milk concentrations “mirrored” plasma concentrations closely with no discernible delay between peak times. The average milk‐to‐plasma (M/P) concentration ratio for zaleplon was approximately 0.50 over the time course. 5‐oxo‐zaleplon was undetectable in all but one milk sample. The maximum exposure of an infant to zaleplon during a feeding at peak milk concentrations was estimated to range from 1.28 μg to 1.66 μg, corresponding to 0.013% to 0.017% of the maternal dose or 0.320 μg/kg to 0.415 μg/kg for a 4 kg infant. The results indicate that zaleplon taken by a nursing mother is transferred through breast milk to her infant in very small quantities that are unlikely to be clinically important.