Pharmacokinetics of Pergolide Mesylate in Horses

Abstract

AimsPergolide mesylate is the treatment of choice for equine pituitary pars intermedia dysfunction (PPID) and veterinary preparations are now licensed for this use in a number of countries. Pharmacokinetic properties of the drug have not been established completely in horses and current dosing recommendations are based upon clinical experience. This study aimed to establish the pharmacokinetic properties of the drug following intravenous administration.MethodsEight healthy Thoroughbred or Standardbred geldings were administered 0.02 mg/kg bwt pergolide mesylate via an intravenous jugular catheter. Blood samples were collected over a period of 48 h from a catheter in the contralateral jugular vein for determination of plasma pergolide concentrations. Pergolide concentrations in plasma were determined using a high‐performance liquid chromatography–tandem mass spectrometry assay. Maximum concentration of pergolide was determined directly from the data. Other pharmacokinetic parameters were determined for each horse by use of noncompartmental analysis with a commercial software program. Area under the curve was calculated by the linear trapezoidal rule. The terminal elimination rate constant and terminal half‐life were calculated by means of log‐linear regression. Initial volume of distribution, mean residence time, and clearance were calculated using standard noncompartmental formulae.ResultsSee Table . Results Mean (± s.d.) Maximum concentration (Cmax) 14.90 ± 5.02 Terminal elimination rate constant (λ) (h−1) 0.14 ± 0.06 Terminal half‐life (h) 5.80 ± 2.26 Area under the curve 0‐∞ (ng*h/ml) 18.63 ± 7.30 Mean residence time (h) 6.30 ± 2.43 Clearance (ml/h/kg bwt) 964.30 ± 460.95 Initial volume of distribution (l/kg bwt) 1.13 ± 0.39 ConclusionsVolume of distribution and half‐life for pergolide in horses are shorter than reported previously. There is no rationale for administering a loading dose of pergolide mesylate; however, based on its pharmacokinetic properties twice daily dosing with pergolide mesylate may be more appropriate than once daily dosing.Ethical animal researchApproved by the Animal Care and Ethics Committee, Charles Sturt University. Sources of funding: Internal funding. Competing interests: Although not used in the current study, David Rendle has acted as a paid speaker and consultant for Boehringer Ingelheim, manufacturers of Prascend: the licensed form of pergolide in Europe and the USA.