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BACKGROUND Donkeys with clinical signs of PPID are treated with oral pergolide mesylate despite the lack of species-specific pharmacokinetic data. OBJECTIVES To evaluate the pharmacokinetics of intragastric and oral pergolide mesylate in healthy donkeys (Equus asinus). STUDY DESIGN Pharmacokinetic study. METHODS Six healthy donkeys were administered pergolide mesylate [Prascend®] at 2 μg/kg bodyweight (bwt) intragastrically once, then once daily per os (PO) for 5 days. Blood samples were collected at 0, 10, 20, 30, 45 min and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h after the single intragastric dose, once daily immediately before the PO dose, and then again at the above times after day 5 of once daily oral dosing. Plasma pergolide concentration was quantified via ultra-performance liquid chromatography-tandem mass spectrometry. Pergolide concentration versus time data after the first and last doses were analysed based on noncompartmental pharmacokinetics using commercial software. Paired t-tests were used to compare single and multiple doses (P<0.05). In a follow-up study, a single oral dose was then administered to two donkeys followed by concurrent blood sampling from the jugular and cephalic veins to evaluate the effect of route of administration on pergolide pharmacokinetics. RESULTS Cmax , Tmax , AUC, and t½λz differed significantly (P<0.03) after single and multiple doses, with significantly lower Cmax (0.16 ± 0.16 ng/ml) and t½λz (9.74 ± 1.35 h) after intragastric dosing on Day 1 than after 5 days of oral dosing (3.74 ± 2.26 ng/ml and 16.35 ± 5.21 h, respectively). Pergolide plasma concentrations were higher in jugular vein samples compared to cephalic vein samples after a single oral dose. MAIN LIMITATIONS Small sample size; varied administration routes. CONCLUSIONS Pergolide mesylate (dosed at 2 μg/kg bwt) is bioavailable in donkeys after intragastric and PO administration. Differences in pharmacokinetics were noted after multiple doses, likely related to different routes of administration and sublingual absorption of pergolide. This article is protected by copyright. All rights reserved.