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Methimazole is an oral antithyroid compound that exhibits a skin-depigmenting effect when used topically. However, the effect of topical methimazole on thyroid function has not been reported. This study was aimed at assessing the safety of topical methimazole used to treat pigmented lesions, without affecting thyroid hormones due to systemic delivery. The pharmacokinetics of methimazole, either applied in the form of a 5% topical formulation to facial skin or taken orally in the form of a 5-mg tablet by 6 volunteers, were determined. In addition, the effect of long-term topical applications of 5% methimazole on the function of the thyroid gland in 20 patients with epidermal melasma was determined following 6 weeks of once-daily application. Cutaneous adverse effects of topical methimazole were determined. From 15 min up to 24 h after application, methimazole was undetectable in the serum of the individuals …