Pharmacokinetics of pergolide in normal mares

Abstract

Objective: To determine the pharmacokinetic properties of oral pergolide in normal mares. Animals: 6 horses, 3-17 years of age, 355-582 kg Procedures: In a randomized, cross over design six healthy adult female horses received pergolide (PO) 0.01mg/kg or placebo after 8 hours of fasting. Samples were taken over a period of 6 day for each portion of the study (treatment or placebo) with a two week minimum wash out period between study periods. Quantification of pergolide concentration was determined by UPLC-MS. Quantification of α-MSH was determined by radioimmunoassay validated for horses. Quantification of ACTH concentration was determined by chemiluminescent enzyme immunoassay. Results: Pergolide was detected in all treated horses. The relatively short time to peak concentration (0.5 hours) indicates a rapid absorption. Mean maximum concentration measured was 4.05 ng/ml + 2.02 with a median time to maximum concentration being 0.415 hours (range:0.33-1.0). The mean half life of pergolide was determined to be 5.86 hours + 3.42. Lower limits of quantitation for the UPLC-MS assay was 0.5 ng/ml. α-MSH results were evaluated using a multiple analysis of variance assay for repeated measures comparing treatment, time, and period. There was a significant treatment to period effect with p=0.02. The effect of period appears to be more significant (p=0.06) compared to the effect of treatment (p=0.77). No effect from pergolide was noted on ACTH concentrations. Conclusions and Clinical Relevance: Horses appear to absorb and eliminate pergolide more rapidly than previously expected. Based on this pharmacokinetic data the dosing strategies of pergolide may need to be altered. However, assay sensitivity does need to be improved prior to recommendations being made.