Distribution of Alprazolam Into the Milk of Lactating Mares and Subsequent Absorption by Nursing Foals

Alprazolam is used to facilitate mare-foal bonding in aggressive or anxious postpartum mares. In humans, alprazolam crosses the blood-milk barrier, but the amount transferred into milk is minor and compatible with breastfeeding as the relative infant dose is < 10%. Similar data are not available for horses. The aim of this study was to measure alprazolam in serum and milk of mares (milk: serum ratio) administered alprazolam, and to determine alprazolam serum concentrations in nursing foals to estimate the extent of absorption. This was a prospective observational study involving 7 healthy postpartum mares and foals. Mares received alprazolam (0.04 mg/kg PO, q12h) for 6 days. Venous blood and milk samples were collected on days 3,4,5 and 6, just before the next dose, and were used to calculate milk: serum ratios and estimate the extent of absorption of alprazolam by foals. A validated liquid chromatography-tandem mass spectrometry assay was used to measure alprazolam and α-hydroxyalprazolam. There were no significant differences in concentrations of alprazolam or α-hydroxyalprazolam in mare serum, milk, or foal serum over time, consistent with steady state and a lack of accumulation. Milk:serum ratios were similar to slightly higher than those reported in humans (median: 0.64; range: 0.42-3.0). Relative foal dose (RFD) based on 12 h concentrations was < 10% in all foals and in 96% of total samples. Foal serum concentrations of alprazolam were 6.6% ± 4.1% of those in mare serum at the same time points. This study shows that milk:serum ratios of alprazolam in mares are variable. Foal serum concentrations and RFD suggest that alprazolam is safe for use in mares with nursing foals.