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

The research investigates the pharmacokinetics and pharmacodynamics of orally-administered pergolide in horses suffering from pituitary pars intermedia dysfunction.

Study Design and Methodology

• The research was conducted as a non-randomized clinical trial involving six horses diagnosed with pituitary pars intermedia dysfunction (PPID) through thyrotropin-releasing hormone (TRH) stimulation tests.
• These horses were treated with pergolide, administered orally at a dose of 4 μg/kg for 18 days.
• Plasma samples were collected at three different intervals – 0.5 h before, and 2 and 12 h after each pergolide administration – for determining the concentrations of pergolide and Adrenocorticotropic hormone (ACTH).

Key Findings

• Results showed that the maximum plasma concentrations after the initial oral dose of pergolide were not significantly different from the maximum steady-state concentration at day 18 of the trial.
• Chronic administration of the drug was not associated with drug accumulation, with pergolide concentration reaching a steady state within 3 days.
• Interestingly, concentrations of pergolide were observed to fluctuate considerably throughout the trial, with peak concentrations being four times higher than trough ones.
• It was observed that plasma ACTH concentration decreased significantly within 12 h of administration, with further reduction over the course of 10 days from the onset of treatment.

Interpretation and Implications

• Although there were fluctuations in pergolide and ACTH concentrations, timing of the ACTH measurement in relation to pergolide administration did not significantly affect the measurement outcome.
• Changes in response to TRH were noted at the 8-day mark, with no further change being identified at 18 days.
• Despite the study being limited by the small number of horses, the findings showed that oral pergolide significantly suppresses PPID activity within hours.
• The researchers concluded that to reduce the level of ACTH fluctuation, administering pergolide as a twice-daily dose could be more suitable, given the pergolide concentration’s consistent fluctuations indicating a terminal elimination half-life of less than 12 hours.