Twice-daily drugs for Cushings horse may be more effective, researchers say

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Cushing's disease in horses commonly causes excessive hair growth, muscle wasting along the top line, and abnormal fat distribution.
Cushing’s disease in horses commonly causes excessive hair growth, muscle wasting along the top line, and abnormal fat distribution.

Twice-daily dosing of pergolide may be more effective for horses affected by Pituitary Pars Intermedia Dysfunction (PPID or Cushings Disease) than the manufacturer-recommended once-a-day treatment, researchers say.

PPID is one of the most common endocrine (hormonal) disorders of horses and ponies. Typically, older animals are affected. If left untreated, many cases develop laminitis.

Overactivity of the pars intermedia (middle lobe) of the pituitary gland results in increased adrenocorticotrophic hormone (ACTH) in the plasma. The baseline level of plasma ACTH is often used to diagnose PPID. This may not give a definitive result, and a dynamic “TRH stimulation test” may sometimes be used.

Pergolide is commonly used to treat horses and ponies with PPID. It is thought that PPID is due to degeneration of the nerves that inhibit the activity of the pars intermedia of the pituitary. Pergolide may mimic or replace this lost inhibition and so reduce the ACTH production.

Pergolide is typically administered once daily in accordance with the product data sheet provided by the manufacturer.

Research carried out at Charles Sturt University, Wagga Wagga, New South Wales, Australia, and published recently in Domestic Animal Endocrinology, investigated the effect of oral pergolide in PPID-affected horses.

Six horses with PPID were included in the study. They received daily doses of pergolide (at 4µg/kg) once a day for the duration of the study, which lasted 18 days. Blood samples to monitor pergolide and ACTH were collected 30 minutes before, and 2 and 12 hours after pergolide administration.

The research team found that oral pergolide had a rapid effect on plasma ACTH concentration, producing significant suppression of pars intermedia activity within hours. The plasma ACTH concentration reduced significantly within 12 hours of administration. Further reductions occurred up to 10 days after treatment started.

Fluctuations in the pergolide levels suggested that the drug was rapidly removed from the blood, with an elimination half-life of fewer than 12 hours. This could account for similar fluctuations in ACTH concentration.

The authors of the report suggest that to reduce the fluctuation of ACTH levels, twice-daily dosing of pergolide may be more appropriate.

Pharmacokinetics and pharmacodynamics of pergolide mesylate after oral administration in horses with pituitary pars intermedia dysfunction. Rendle DI, Doran G, Ireland J, Edwards S. Domest Anim Endocrinol. (2019) 68; p135-141. 

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