Pharmacokinetic properties of pergolide mesylate following single and multiple-dose administration in donkeys (Equus asinus).
Authors: Xue Cynthia, Davis Jennifer, Berghaus Londa J, Hanafi Amanda, Vaughn Sarah A, Hart Kelsey A
Journal: Equine veterinary journal
Summary
# Editorial Summary: Pergolide Pharmacokinetics in Donkeys Pergolide mesylate is routinely prescribed to donkeys with pituitary pars intermedia dysfunction (PPID), yet evidence-based dosing guidance for this species has been lacking until now. Researchers administered pergolide at 2 µg/kg to six healthy donkeys via intragastric tube initially, then orally for five consecutive days, collecting plasma samples over 48 hours and analysing drug concentrations using liquid chromatography–mass spectrometry to establish species-specific pharmacokinetic parameters. Peak plasma concentrations increased substantially between day one intragastric administration (0.16 ng/ml) and day five of oral dosing (3.74 ng/ml), alongside a marked lengthening of elimination half-life from 9.74 to 16.35 hours, suggesting cumulative bioaccumulation with repeated oral dosing. Crucially, jugular venous samples showed higher pergolide concentrations than cephalic samples following oral administration, indicating significant sublingual absorption—a route-dependent phenomenon that may explain variable clinical responses to treatment. These findings provide donkey practitioners with the first pharmacokinetic evidence base for pergolide dosing and highlight the importance of assessing plasma concentrations from appropriate sampling sites when monitoring drug levels, whilst also warranting consideration of potential drug accumulation with standard once-daily oral protocols in clinical PPID management.
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Practical Takeaways
- •Pergolide mesylate can be used to treat donkeys with pituitary pars intermedia dysfunction, though pharmacokinetics differ between single and multiple dosing
- •Oral dosing achieves higher plasma concentrations than intragastric administration, likely due to sublingual absorption in donkeys
- •Accumulation occurs with repeated daily dosing, which may affect steady-state drug levels and clinical efficacy in donkeys
Key Findings
- •Pergolide mesylate at 2 μg/kg is bioavailable in donkeys via both intragastric and oral routes
- •Cmax was significantly lower after single intragastric dose (0.16 ng/ml) compared to after 5 days of oral dosing (3.74 ng/ml)
- •Half-life was significantly shorter after single intragastric dose (9.74 h) versus multiple oral doses (16.35 h)
- •Jugular vein pergolide concentrations were higher than cephalic vein samples, suggesting sublingual absorption contributes to oral bioavailability