Pyrilamine in the horse: detection and pharmacokinetics of pyrilamine and its major urinary metabolite O-desmethylpyrilamine.

This study analyses the detection and pharmacokinetics of an antihistamine known as pyrilamine, and its major urinary metabolite O-desmethylpyrilamine, in horses. The researchers found that pyrilamine was not highly bioavailable when administered orally and could be detected in urine for up to a week after a single dosage.

Introduction

• Pyrilamine is an antihistamine that is used in both human and veterinary medicine.
• Antihistamines affect the central nervous system in horses, which means that pyrilamine can potentially affect a racing horse’s performance.
• The primary objective of the study was to investigate how pyrilamine and its major urinary metabolite, O-desmethylpyrilamine (O-DMP), behaved in the horse’s body, particularly after it was administered intravenously or orally.

Methodology

• The researchers administered pyrilamine to horses in two ways: by an intravenous injection (I.V.) and orally.
• In each case, the dose was 300 mg per horse.
• They monitored the serum concentration of pyrilamine for varying time periods post-dosing.
• Additionally, the levels of O-DMP were observed in urine samples up to 168 hours (1 week) post-dosing.

Results

• Serum concentrations of pyrilamine significantly declined from approximately 280 ng/mL at 5 minutes post-dose to about 2.5 ng/mL at 8 hours post-dose when given intravenously.
• When given orally, the serum concentration of pyrilamine peaked at about 33 ng/mL at 30 minutes, dropping to less than 2 ng/mL at 8 hours post-dose.
• Pyrilamine was not detected in the serum 24 hours after administration by either method.
• After I.V. injection of pyrilamine, O-DMP was recovered from urine at a level of about 20 microg/mL at 2 hours post-dose, dropping to about 2 ng/mL at 168 hours post-dose.
• The concentration of O-DMP peaked at about 12 microg/mL at 8 hours post-dose and decreased to less than 2 ng/mL at 168 hours post-dose after oral administration.

Conclusion

• The bioavailability of pyrilamine is low when administered orally, estimated to be only 18%.
• Using sensitive enzyme-linked immunosorbent assay tests, pyrilamine could be detected in urine for up to a week after a single administration.
• Based on this data, researchers suggest that the withdrawal period for pyrilamine after repeated oral administrations may need to be at least a week to ensure the substance is fully eliminated from the horse’s system.