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

Abstract:

Background: Alprazolam is a benzodiazepine 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; the relative infant dose is <10%. Similar data are not available for horses. Hypothesis/

Objectives: To measure alprazolam in serum and milk of mares (milk:serum ratio) administered alprazolam, and to determine serum concentrations of alprazolam in nursing foals to estimate extent of absorption.Animals: 7 healthy post-partum mares and foals.

Methods: Prospective observational study. 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 its metabolite, -hydroxyalprazolam.

Results: There were no significant differences in concentrations of alprazolam or -hydroxyalprazolam in mare serum, milk or foal serum over time. Milk:serum ratios were similar to higher than those reported in humans (median:0.64; range:0.42-3.0). Relative foal dose (RFD) based on 12h 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. Conclusions and clinical importance: 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.