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

Abstract

The objective of this study was to gain an understanding of the pharmacokinetic and pharmacodynamic properties of pergolide in horses with PPID after of long-term oral administration. Six horses with confirmed PPID were treated with pergolide (Prascend ) at 1 mg/horse po q24 h for 2 months, followed by 2 mg/horse po q24 h for 4 months. Following the last dose, plasma samples were collected for measurement of pergolide using an LC/MS/MS method and ACTH measurement using a chemiluminescent immunoassay. Noncompartmental and compartmental pharmacokinetic analyses were performed, as well as pharmacodynamic assessment of the effect of plasma pergolide concentrations on plasma ACTH concentrations. Pergolide effectively decreased plasma ACTH concentration in aged horses with PPID, with similar pharmacokinetic properties as reported in young horses, including an approximate terminal half-life of 24 h. Plasma ACTH concentration increased by 50% in 3/6 horses at 2 days and 6/6 horses 10 days after discontinuing drug administration. Pergolide was quantified in all horses at 2 days and in none at 10 days after last dose. In summary, after discontinuing pergolide treatment, plasma ACTH concentration increased while pergolide was still quantifiable in some horses. Once-daily dosing of pergolide is likely appropriate in most horses with PPID for regulating the plasma ACTH concentration.

Factors associated with survival, laminitis and insulin dysregulation in horses diagnosed with equine pituitary pars intermedia dysfunction

“…Treatment with pergolide was strongly associated with survival. This finding is consistent with previous reports that established pergolide as the treatment of choice for PPID . In Australia, two forms of pergolide are approved for use in horses, a liquid form and a tablet form.…”

Equine pituitary pars intermedia dysfunction: current understanding and recommendations from the Australian and New Zealand Equine Endocrine Group

“…The dose of pergolide should be increased until clinical signs have greatly improved and test results have at least dramatically improved or ideally normalised. Daily dosing is recommended because the half‐life ranged from 5.6 to 60 h in a single‐dose study, and was approximately 24 h in a chronic‐dosing study . In the chronic‐dosing study, six horses with confirmed PPID were administered pergolide at 0.002 mg/kg PO every 24 h for 2 months, followed by 0.004 mg/kg PO every 24 h for an additional 4 months.…”

“…Daily dosing is recommended because the half‐life ranged from 5.6 to 60 h in a single‐dose study, and was approximately 24 h in a chronic‐dosing study . In the chronic‐dosing study, six horses with confirmed PPID were administered pergolide at 0.002 mg/kg PO every 24 h for 2 months, followed by 0.004 mg/kg PO every 24 h for an additional 4 months. Plasma ACTH concentration increased by 50% in three of the six horses 2 days after the last dose and in all six horses by 10 days after the last dose.…”

“…There is also evidence that a higher concentration of pergolide may be warranted during the dynamic phase of the ACTH circannual cycle to control clinical signs and normalise ACTH concentrations more rapidly . Mildly affected animals may only require treatment around the acrophase, which may allow for these horses to compete in equine athletic events that perform drug testing at other times of the year.…”

“…Plasma ACTH can be rechecked in 30 days to identify spurious elevations or assess the response to treatment. During the dynamic period, clinical signs and ACTH concentration may not substantially improve with standard doses of pergolide until the onset of the quiescent period . In such cases, it may be necessary to more aggressively titrate the dose if more rapid and substantial regulation is desired .…”