The Efficacy and Safety of a Novel Lipophilic Formulation of Methimazole for the Once Daily Transdermal Treatment of Cats with Hyperthyroidism

Abstract

Background: Previous studies on transdermal methimazole have used pluronic lecithin organogel as the vehicle. This might not be the most suitable vehicle for a lipophilic drug, such as methimazole.Hypothesis/Objectives: Once daily transdermal administration of a novel lipophilic formulation of methimazole is as safe and effective as oral carbimazole in treating hyperthyroidism in cats.Animals: Forty-five client-owned cats diagnosed with hyperthyroidism. Methods: Prospective study. Cats with newly diagnosed, untreated hyperthyroidism were treated with carbimazole (5 mg PO, q12h) or methimazole (10 mg) applied to the inner pinnae q24h. Cats were examined after 0, 1, 4, 8, and 12 weeks of treatment. Clinical signs, body weight, systolic blood pressure, hematologic, serum biochemical and urine parameters, total serum thyroxine concentrations (TT4), and serum methimazole concentrations were recorded.Results: No significant differences between groups were detected at day 0. Both formulations were effective in treating hyperthyroidism. No significant differences were detected in thyroxine concentrations, body weight, blood pressure, heart rate, alkaline phosphatase, alanine aminotransferase, creatinine, urea, and urine specific gravity (USG) between groups. The serum methimazole concentrations correlated poorly with TT4-concentrations in both groups.Conclusions and Clinical Importance: In this 12-week trial, once daily application of a novel formulation of transdermal methimazole applied to the pinnae was as effective and safe as twice daily oral carbimazole in the treatment of cats with hyperthyroidism. This novel formulation and transdermal application could have practical advantages to some pet owners.

Biophysical parameters of rats’ skin after the administration of methimazole

“…However, after local methimazole administration, a species-specific reaction to the is demonstrated. In humans, it induces skin discoloration (17) and inhibits keratinocyte proliferation (7), which was not observed in cats (15). A significant influence of methimazole on melanocyte functions appears (17,19) despite the lack of cytotoxicity even in high concentrations (2).…”

“…Methimazole (1-methyl-2-mercapto imidazole) is an antithyroid drug used worldwide as the first choice in chronic treatment of hyperthyroidism in humans (31), dogs (39), and cats (15,16,21,28,29). Its mechanism of action is similar to other thioamides that block the activity of thyroperoxidase, leading to reduced biosynthesis of thyroid hormones; however, uncontrolled methimazole treatment (overdosing) results in hypothyreosis (5).…”

“…post-inflammatory hyperpigmentation (17) and psoriasis (10). In cats subcutaneous treatment of hyperthyreosis with methimazole also did not cause any local side effects (15), but auricular erythema was reported. This type of treatment was not accompanied by facial pruritus, which could be noted in the case of oral administration (15).…”

Management and monitoring of hyperthyroid cats: a survey of Australian veterinarians

“…Transdermal methimazole was often used by respondents to our survey. It is thought to improve client compliance, 14,25 but a study evaluating long-term transdermal methimazole use found 17% of owners admitted not treating their cat regularly, suggesting compliance may still be suboptimal. 26 Adverse reactions of anti-thyroid medications were consistent with previous reports.…”

Influence of Beta-Endorphin on Oxygen Activity of Neutrophils and Total Antioxidant Status in Rats after Chronic Administration of Methimazole

“…It also protects tissues against lipid peroxidation, stimulating the mechanisms of the antioxidant system (16,23,35). Methimazole is an anti-thyroid drug commonly used around the world in the long-term treatment of hyperthyroidism in humans (11,15,27,39), dogs (37), and cats (12,13,18,24,25,36). Like in other thionamides, its mode of action is based on blocking the activity of thyroid peroxidase, which leads to a decrease in the synthesis of thyroid hormones (6).…”