Distribution of Alprazolam Into the Milk of Lactating Mares and Subsequent Absorption by Nursing Foals.
Abstract: 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.
© 2025 John Wiley & Sons Ltd.
Publication Date: 2025-04-14 PubMed ID: 40229923DOI: 10.1111/jvp.13509Google Scholar: Lookup
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Summary
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This research investigates how Alprazolam, a medication used to support mare-foal bonding in horses, transfers into the milk of nursing mares and is subsequently absorbed by the foals. The findings suggest minimal absorption by foals, hinting that Alprazolam use may be safe for nursing horses.
Objectives of the Research
- The study aimed to determine the extent of Alprazolam’s transmission into mare milk and its subsequent absorption by nursing foals.
- The researchers hoped to establish an equivalent understanding for horses to what is established for humans, where Alprazolam is known to cross the blood-milk barrier but does so in minor, breastfeeding compatible quantities.
Methodology
- This was a prospective observational study involving seven healthy postpartum mare and foal pairs.
- The mares were administered oral Alprazolam every 12 hours for six days, and venous blood and milk samples were collected between day 3 and 6, prior to the next dose application.
- The research team used a validated liquid chromatography-tandem mass spectrometry assay to measure Alprazolam and α-hydroxyalprazolam concentrations in the samples, enabling them to calculate milk: serum ratios and estimate the foals’ absorption level.
Findings
- Neither the alprazolam nor the α-hydroxyalprazolam levels varied significantly in the mare serum, milk, or foal serum over time, demonstrating consistent levels and absence of accumulation.
- The calculated milk:serum ratios were typically similar or slightly higher than those documented in human studies, with a median of 0.64 and ranging between 0.42 and 3.0.
- The relative foal dose (RFD) based on 12-hour concentrations was < 10% for all foals and made up less than 10% in 96% of the total samples.
- Foal serum concentrations of Alprazolam were around 6.6% ± 4.1% of those in mare serum at the same time points.
Conclusion
- The research concludes that the milk:serum ratios of Alprazolam in mares vary, but the low serum concentrations and RFD in foals suggest that it is safe to administer Alprazolam to mares nursing foals.
- These findings are crucial for animal care, particularly in managing mare-foal relationships and ensuring minimal risks associated with medication use during the postpartum nursing period.
Cite This Article
APA
Quattrini C, Knych HK, Magdesian KG.
(2025).
Distribution of Alprazolam Into the Milk of Lactating Mares and Subsequent Absorption by Nursing Foals.
J Vet Pharmacol Ther.
https://doi.org/10.1111/jvp.13509 Publication
Researcher Affiliations
- William R. Pritchard Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California, Davis, USA.
- K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, California, USA.
- Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, USA.
Grant Funding
- University of California, Center for Equine Healthy, School of Veterinary Medicine
- Roberta A and Carla Henry Endowed Chair in Emergency Medicine and Critical Care, School of Veterinary Medicine, University of California Davis
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