Pergolide is a synthetic ergot derivative and is a potent, long-acting dopamine receptor agonist. Both in vitro and in vivo pharmacological studies have demonstrated the activity of pergolide as a selective dopamine agonist with little or no effect on norepinephrine, epinephrine or serotonin pathways at therapeutic doses. As with other dopamine agonists, pergolide inhibits the release of prolactin. In horses with Pituitary Pars Intermedia Dysfunction (PPID) pergolide exerts its therapeutic effect by stimulating dopamine receptors. Further, in horses with PPID, pergolide has been shown to decrease the plasma levels of ACTH, MSH and other pro-opiomelanocortin peptides.
Pharmacokinetic information in the horse is available for oral doses of 2 µg pergolide/kg body weight and 10 µg pergolide/kg body weight. It has been demonstrated that Pergolide is rapidly absorbed with a short time to peak concentration.
Peak concentrations (Cmax) following the dose of 10 µg/kg were low and variable with a mean of ~ 4 ng/mL and a mean terminal half life (T1/2) of ~ 6 hours. The median time of peak concentration (Tmax) was ~0.4 hrs and the area under the curve (AUC) was ~ 14 ng*h/ml. The terminal half life in this study was much shorter than reported in humans. This is likely due to the sensitivity of the analytical assay in this study which did not allow for complete elucidation of the concentration - time profile. Therefore the rapid estimated rate of elimination in this study may not be a true reflection of the elimination phase.
In a more sensitive analytical assay, plasma concentrations following the dose of 2 µg pergolide/kg were very low and variable with peak concentrations ranging from 138 to 551 pg/ml. The peak concentrations occurred at 1.25 +/- 0.5 hours (Tmax). Plasma concentrations in most horses were quantifiable for only 6 hours post dose. However, one horse had quantifiable concentrations through 24 hours. Terminal half-lives were not calculated as there was incomplete elucidation of the plasma concentration-time curve for most horses. Pergolide mesylate is approximately 90 % associated with plasma proteins in humans and laboratory animals.