Pharmacokinetics and pharmacodynamics of oral pergolide mesylate in horses with pituitary pars intermedia dysfunction

Reasons for performing study: The pharmacokinetics and pharmacodynamics of pergolide in horses are poorly understood.
Objectives: Investigate pharmacokinetic and pharmacodynamic properties of orally administered pergolide in horses with pituitary pars intermedia dysfunction (PPID).
Study design: Cohort study.
Methods: Six horses with PPID received 4 μg/kg oral pergolide for 18 days. Samples were collected 0.5 h before and 2 and 12 h after administration of pergolide daily for 18 days and plasma pergolide and adrenocorticotropic hormone (ACTH) concentrations were determined.
Results: Maximum plasma concentrations after the first oral dose of pergolide (0.104–0.684 ng/mL; mean 0.308 ± 0.201 ng/mL) were not significantly different to the maximum steady state concentration at Day 18 (0.197–0.628 ng/mL; mean 0.336 ± 0.159 ng/mL). A marked difference between mean plasma peak and trough concentrations of pergolide remained throughout the study. Pergolide concentration reached steady state within 3 days and the drug did not accumulate (R = 1.09). Plasma ACTH concentration reduced significantly within 12 h of the first dose of pergolide with further reductions occurring over the next 10 days. Although there were parallel fluctuations in the concentrations of pergolide and ACTH, timing of ACTH measurement in relation to the administration of pergolide did not have a significant effect.
Conclusions: Oral pergolide rapidly suppresses the pars intermedia in horses with PPID. Follow‐up testing may be possible earlier than is employed currently. More frequent dosing may reduce fluctuation in pergolide and ACTH concentrations, which might have implications for patient monitoring.