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tvpjournal.com FOCUS ON PHARMACOLOGY Peer reviewed Today's Veterinary Practice July/August 2014 38 M ethimazole is commonly used for the pharmacologic management of feline hyperthyroidism. 1 This article reviews the properties of methimazole that are of impor- tance to practitioners treating this common endocrinopathy. PROFILE OF MEDICATION Classification This compound belongs to the imidazole- thiones. These aromatic compounds con- tain an imidazole ring, which bears a thio- ketone group. Methimazole (1-methylimid- azole-2-thiol; Figure) is a white, crystalline substance that is freely soluble in water. The chemical formula is C 4 H 6 N 2 S; molecu- lar weight is 114.16 daltons. Carbimazole, which is also used in the treatment of hyperthyroidism in cats, is a prodrug, which is converted to methimazole in the liver. Mechanism of Action Pharmacodynamics. Methimazole is a thioureylene anti- thyroid agent that inhibits formation of thyroid hormones by interfering with the incorporation of iodine into tyrosyl resi- dues of thyroglobulin. This process takes place by interfering with oxidation of iodide ion and iodotyrosyl groups through inhibition of the peroxidase enzyme. However, it does not affect the thyroid gland's ability to trap inorganic iodide or release preformed hormones (T3 and T4). Methimazole has also been shown to inhibit vitamin K epox- ide reductase, which can lead to bleeding disorders characterized by a prolonged PIVKA (proteins induced by vitamin K absence or antagonism) and, rarely, a prolonged prothrombin time. Pharmacokinetics. Methimazole is minimally protein bound, MethiMazole Management of Feline hyperthyroidism David Bruyette, DVM, Diplomate ACVIM (Internal Medicine) VCA West Los Angeles Animal Hospital & Veterinary Diagnostic Investigation and Consultation Feline Friendly Article metabolized in the liver, and excreted primarily in the urine. In cats, oral methimazole is rapidly absorbed, with: • An oral bioavailability of 93% • Maximal serum concentrations seen within 1.5 hours • Mean half-life of 3.12 hours and serum concentra- tions at 24 hours—after a single oral 5-mg dose— of 21.7 ± 28.9 ng/mL. 2 See Transdermal Methimazole: How Does It Measure Up? for more information on this route of administration and its mechanism of action. APPLICATION IN VETERINARY MEDICINE Indications Methimazole is FDA-approved for the treatment of hyperthyroidism in cats. It may also be used to con- trol hyperthyroidism in dogs with functional thyroid tumors (off-label use). Methimazole (Felimazole, dechra-us.com) is ap- proved for use in the U.S. and other countries, while carbimazole (Vidalta, merck-animal-health.com) is approved for use outside the U.S. Contraindications Methimazole should not be used in cats with: 1. Hypersensitivity to methimazole, carbimazole, or the excipient, polyethylene glycol 2. Coagulopathies or hematologic disorders, such as ane- mia, neutropenia, lymphopenia, or thrombocytopenia 3. Primary liver disease or renal failure (or use cautiously) 4. Pre-existing autoimmune disease because autoim- mune disorders (see Adverse Effects, page 40) have been reported in cats taking methimazole. Methimazole should also not be used in preg- Figure. Chemical struc- ture for methimazole (1-methylimidazole-2-thiol).