Methimazole administration to cats : in vivo and in vitro studies of transdermal absorption : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Veterinary Science at Massey University, Manawatu, New Zealand
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Date
2015
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Massey University
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Abstract
The use of medications formulated as ointments or gels and applied to the inner pinna of
cats has become popular in veterinary medicine due to the ease of administration by this
route compared to oral administration. Benign hyperplasia of the thyroid is a very
common condition in cats older than ten years of age. Medical therapy with anti-thyroid
drugs such as methimazole or the pro-drug of methimazole, carbimazole, is one of the
treatment options for cats with hyperthyroidism. All previous studies of methimazole
applied to the inner ear of cats have used Pluronic® lecithin organogel as the vehicle,
however carbimazole and methimazole are lipophilic drugs, and PLO gel might not be
the most suitable vehicle for a lipid soluble drug.
A series of studies were designed to test a new, lipophilic formulation of carbimazole
and subsequently a new formulation of methimazole for transdermal application to the
inner ear of cats for the therapy of hyperthyroidism. Two pharmacokinetic studies in
healthy cats, one pilot trial and one clinical trial in client owned hyperthyroid cats,
established that the lipophilic formulation could be absorbed from the ear and was a safe
and efficacious therapy for hyperthyroidism in cats. A drug company (Bomac Ltd, now
Bayer NZ Ltd) was interested in the novel formulation and the product was patented
(International Application Number PCT/NZ2008/000011). The commercial product
containing the drug and vehicle was sold in New Zealand as Hyper-T™ Earspot.
Finally, a series of three in vitro studies were performed to determine that methimazole
in the lipophilic vehicle was: a) absorbed across the pinnal skin; b) absorbed more
completely at that site than the same formulation applied to the neck, groin or thoracic
skin; and c) able to penetrate from the inner to the outer ear of cats in an in vitro model.
These studies represent the most extensive studies to date of a drug applied to the inner
pinna of cats. The results from these studies suggest that methimazole in a lipophilic
vehicle can be absorbed across the skin of cats and is an efficacious therapy for the
treatment of hyperthyroidism in cats.
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Keywords
Cats, Diseases, Treatment, Hyperthyroidism, Veterinary pharmacotherapy