South African Equine Veterinary Association Congress 2015 Protea Hotel Stellenbosch
In humans with pituitary gland macroadenomas (notably prolactinomas), dopaminergic agonist
therapy has goals of both reducing excessive hormone secretion as well as decreasing tumour size
to correct visual and other neurological deficits caused by the mass effect of the tumour. In a
group of horses that had pituitary gland size determined by computed tomography (CT) before
and after 6 months of pergolide treatment, no decrease in pituitary gland size was found.
However, this study was potentially confounded by effect of season as the post-treatment CT
scans were performed in August and September when activity of the hypothalamic-pituitary axis
and pars intermedia and total pituitary gland size naturally increase with hormonal activity in
preparation for winter.
Until 2007, pergolide had been available in tablet form (0.25-1.0 mg, PermaxTM, Eli Lilly) with
this formulation costing $75-100/month for a treatment dose of 1 mg/day. Because this was not an
inconsequential expense for many retired family pets, several compounding pharmacies started to
market pergolide products as suspensions, granules, or even in treats, often at a cost that was less
than half that of PermaxTM. In 2002, reports started to appear describing development of valvular
heart disease with significant regurgitation in human patients that had been receiving long-term
pergolide for treatment of PD. This complication ultimately led to voluntary withdrawal of
PermaxTM from the marketplace in 2007 and left compounding pharmacies as the only source of
pergolide for PPID-affected equids. Unfortunately, there is limited regulatory oversight of
compounding pharmacies and independent analysis of pergolide products from several
compounding pharmacies revealed considerable variation in potency as well as degradation,
especially of water based drug suspensions, after as little as 2 weeks of storage. Of interest,
considerable variation in pergolide content was even found between different scoops of a
compounded granular formulation taken from the same container.
A final medication that has been used to treat PPID-affected equids is trilostane, a competitive
inhibitor of 3-β-hydroxysteroid dehydrogenase that is being increasingly used for treatment of
pituitary-dependent hyperadrenocorticism in dogs. In one clinical study, trilostane (0.4-1.0
mg/kg, PO, q 24 h in feed) was reported to be effective in reversing both clinical signs (primarily
laminitis) and abnormal endocrinologic test results in a group of PPID-affected horses and
ponies. However, horses and ponies in that study received additional management for laminitis
and the “improvement” in endocrinologic test results was not overly convincing. As with many
chronic diseases in the horse, specific nutrient supplementation and complementary or
alternative therapies, including acupuncture and herb mixtures, have been advocated for equids
with PPID. A product made from chasteberry has been one of the more popular herbs used;
however, a small field study demonstrated that this product was an ineffective treatment for
PPID.
PrascendTM field efficacy study and extended use studies: Because there was both need and
demand for a consistent, high quality pergolide product, Elanco Animal Health, the veterinary
subsidiary of Eli Lilly, designed an open field clinical efficacy study with the goal of having
pergolide approved by the FDA for treatment of equids with PPID. In the midst of the study,
Boehringer-Ingelheim Vetmedica secured the rights to the drug and continued with development
of PrascendTM, a 1 mg scored pergolide mesylate tablet, that was approved by the FDA for
treatment of PPID in equids in the fall of 2011. The open field clinical efficacy study enrolled 122
equids (59 male, 63 female, 10-35 years, 137-623 kg, and 16 breeds) at eight sites. Equids were
enrolled between 11/1/08 and 1/31/09 based on clinical examination and endocrine testing results.
Animals were scored (0-3) for hypertrichosis, hyperhidrosis, polyuria-polydipsia, abnormal fat
distribution, and muscle wasting. Inclusion criteria were a hypertrichosis score >1 and either a
plasma ACTH concentration >50 pg/ml (radioimmunoassay) or failure of endogenous cortisol
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