Pharmacokinetic and pharmacodynamic properties of pergolide mesylate following long-term administration to horses with pituitary pars intermedia dysfunction.

This research paper investigates the properties, effectiveness, and duration of the drug pergolide in managing pituitary pars intermedia dysfunction (PPID) in horses. Six horses with confirmed PPID received an oral dose of pergolide for six months and the study measured the drug’s impact on plasma ACTH concentrations and explored its pharmacokinetic attributes.

Research Method

• The research was conducted on six horses diagnosed with PPID, a neuroendocrine disorder frequently found in elderly horses.
• The horses were administered oral doses of pergolide (1mg per day for the first two months, then 2mg per day for the remaining four months).
• After the last dose, multiple plasma samples were collected from each horse to measure both the level of pergolide and the ACTH concentration.
• Pergolide concentration was measured using a Liquid Chromatography with Tandem Mass Spectrometry (LC/MS/MS), and the ACTH concentration was measured using a chemiluminescent immunoassay.
• Noncompartmental and compartmental pharmacokinetic analyses were carried out to study the drug’s absorption, distribution, metabolism, and excretion in the body. Simultaneously, a pharmacodynamic assessment was done to understand the effect of plasma pergolide concentrations on plasma ACTH concentrations.

Results and Findings

• The study demonstrated that pergolide successfully reduced plasma ACTH concentrations in elderly horses suffering from PPID—this indicates the drug’s efficacy in managing the disorder.
• It was established that the drug’s pharmacokinetics were comparable to those reported in young horses—showing an approximately 24-hour terminal half-life, which indicates once daily dosing is likely appropriate.
• The research also found that plasma ACTH concentration increased by 50% in half of the horses two days after discontinuing the medication and in all horses ten days after discontinuation.
• Pergolide was still detected in all horses’ plasma two days after the last dose was given but was not detected in any of the horses after ten days. This raises an important point about the duration of the drug’s effect and the increase of ACTH concentration even when traces of the drug are present.

In summary

• Results suggest that while discontinuing the pergolide treatment may result in increased plasma ACTH concentration, once-daily dosing of the drug can effectively regulate ACTH concentration in most horses with PPID.
• A crucial revelation, however, is an increase in ACTH concentration even when pergolide was still quantifiable in the horses, which warrants further investigation.
• The study also provides important insights into the pharmacokinetics and pharmacodynamics of pergolide in horses with PPID, which could drive medical decisions and strategies for improving the treatment and management of PPID in horses.