Pars pituitary intermedia dysfunction (PPID) is a common equine geriatric disease that affects approximately 14% of the aged equine population. Pergolide mesylate is the recommended treatment of choice for PPID. However, there are no pharmacokinetic data about the use of pergolide in horses. The objective of this study was to determine the pharmacokinetics of oral pergolide in normal horses.
Six healthy mares (with normal hair coats and a normal dexamethasone suppression test) between the ages of 3-17 years of age were included in the study. Mares were administered either placebo or pergolide (0.01 mg/kg) in a randomized crossover design, with a washout period of approximately 14 days. Mares were fasted for 8 hours prior to administration of the placebo/pergolide. Heparinized blood samples were collected at baseline, and at 0.1, 0.25, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, and 48 hr after administration of placebo/pergolide. Plasma was separated by centrifugation and frozen at -80°C until analysis. Pergolide concentrations were determined by HPLC coupled with electro spray ionization tandem mass spectroscopy. The lowest limit of quantitation (LLOQ) was 0.5 ng/ml.
Results of non-compartmental pharmacokinetic analysis revealed that pergolide is rapidly absorbed with a short time to peak concentration (median Tmax = 0.415 hr). The mean maximum concentration (Cmax) was 4.05 ng/ml ±2.02 ng/ml and the mean terminal half life (T1/2) was 5.86 ± 3.42 hr. The area underneath the curve (AUC) was 14.08 ± 7.46 h*ng/ml. The calculated mean apparent volume of distribution (Vd/F) was 3,082 ± 1,354 ml/kg. The calculated mean apparent oral clearance (CL/F) was 1,204 ml/kg/hr. The pharmacokinetic results indicate that pergolide is more rapidly absorbed and the peak plasma concentrations are much higher than reported in humans. The terminal half life of pergolide in horses (5.86 hr) is much shorter than reported in humans (21 hr). However, the rapid estimated rate of elimination in this study may not be a true reflection of the elimination phase due to the relatively high LLOQ of this assay. Future recommended studies are necessary to determine concentrations and efficacy at steady state.