Thyroid peroxidase (TPO), the enzyme responsible for the iodination and coupling of tyrosine residues in thyroglobulin during thyroid hormone synthesis. Carbimazole, via its active metabolite methimazole, irreversibly inhibits thyroid peroxidase, blocking the incorporation of iodide into thyroglobulin and the formation of triiodothyronine (T3) and thyroxine (T4). The compound also decreases the uptake and concentration of inorganic iodine by the thyroid.

Carbimazole is a prodrug that is rapidly metabolized to methimazole, the active metabolite. Methimazole inhibits thyroid peroxidase, blocking the organification of iodide and the coupling of iodothyronine residues, which suppresses the synthesis of thyroid hormones T3 and T4. Carbimazole also decreases the uptake and concentration of inorganic iodine by the thyroid. The compound has been shown to induce inhibitory phosphorylation of eukaryotic elongation factor 2 (eEF2) associated with inhibition of global protein synthesis.

In vivo, carbimazole is used to treat hyperthyroidism (Graves' disease and other forms of thyrotoxicosis). The compound reduces the production of thyroid hormones T3 and T4, alleviating symptoms of hyperthyroidism. Carbimazole is also used to prepare patients for thyroidectomy. It is administered orally and is rapidly absorbed and metabolized to methimazole.

In vitro enzyme assays for carbimazole involve measuring thyroid peroxidase inhibition using spectrophotometric methods. The enzyme is incubated with iodide and tyrosine substrates and various concentrations of carbimazole or its active metabolite methimazole, and the production of iodinated tyrosine or thyroid hormones is measured. IC50 values are determined from concentration-response curves. These assays confirm the TPO inhibitory activity of carbimazole.

Cellular assays for carbimazole involve treating thyroid cells with the compound or its active metabolite methimazole and measuring thyroid hormone synthesis, iodide uptake, or cell viability. The compound's ability to inhibit thyroid hormone synthesis is demonstrated in these assays. Carbimazole has also been shown to reduce neuronal cell damage in oxygen-deprived human SK-N-SH cells.

In vivo animal studies for carbimazole typically involve administration to rodent or other animal models of hyperthyroidism. The compound's ability to reduce thyroid hormone levels and normalize thyroid function is assessed by measuring serum T3 and T4 levels, thyroid weight, and histopathological examination of the thyroid gland. These studies establish the efficacy and dose-response relationship of carbimazole.

Pharmacokinetic studies of carbimazole show that the compound is rapidly absorbed following oral administration and metabolized to methimazole, the active metabolite. Methimazole distributes to the thyroid gland, where it inhibits thyroid peroxidase. The compound is eliminated primarily by renal excretion. The pharmacokinetic profile of carbimazole supports once-daily or twice-daily dosing for the treatment of hyperthyroidism.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Carbimazole has not yet received marketing approval from the U.S. Food and Drug Administration (FDA), but it is available in other countries. Studies have shown that daily administration of 30 mg or weekly administration of 50 mg of carbimazole has no adverse effects on a small number of breastfed infants. Carbimazole is a prodrug of methimazole, which has been extensively studied during breastfeeding; daily administration of up to 20 mg of methimazole by the mother has not affected thyroid function or intellectual development in breastfed infants. Some experts now recommend that methimazole should be the first-line antithyroid drug for breastfeeding women.
The American Thyroid Association recommends that routine pediatric health assessments should only monitor infant growth and development, and routine serum thyroid function testing is not recommended for children. Rare specific reactions (such as agranulocytosis) may occur, and infants should be closely monitored for signs of infection. If drug-induced blood disorders are suspected, monitoring of the infant's complete blood count and differential count is recommended.
◉ Effects on Breastfed Infants
Eleven mothers took carbimazole orally at doses of 5 to 20 mg daily during pregnancy and 5 to 15 mg daily during lactation (dosage not specified). Serum thyroxine (T4) levels in all 12 infants (including a pair of twins) were not below the lower limit of normal on day 4 postpartum. Thyroid-stimulating hormone (TSH) levels were normal at various time points within 21 days postpartum in all infants.
Four women took carbimazole daily at doses of 10 to 20 mg. Blood samples were collected from infants on days 4, 7, 10, and 42 postpartum, and at 3 and 6 months postpartum. Three infants had normal thyroid function. One infant had elevated TSH levels in the first 10 days postpartum.
One mother of twins started taking carbimazole at 30 mg daily 2 months postpartum. The dose was gradually reduced as thyroid function returned to normal. Infants were breastfed (feeding extent not specified) and underwent clinical and laboratory testing over the next four months. No thyroid dysfunction was detected. Fifteen mothers took 10 to 20 mg of carbimazole daily from 12 to 40 weeks of gestation, with nine continuing this medication during lactation from 2 to 26 weeks. Their infants were monitored for up to 18 months. During this period, the infants' thyroid function was within the normal range, with mean values for thyroid-stimulating hormone (TSH) of 1.4 to 5.9 mIU/L, free triiodothyronine (T3) of 6.2 to 9.3 picomol/L, and thyroxine (T4) of 104 to 189 nanomoles/L. All infants treated with carbimazole had normal results on regular physical examinations from 2 to 18 months, and all six infants assessed at 18 months had normal Griffith Intelligence Scale scores. One mother took 50 mg of carbimazole once weekly during pregnancy and postpartum. Her infant was exclusively breastfed for the first 84 days of life and underwent clinical and laboratory examinations during the first 4 months. Although the infant had slightly increased muscle tone and deep tendon reflexes and was irritable, serum thyroid hormone levels and growth were normal. No symptoms or signs of hypothyroidism were observed.
◉ Effects on breastfeeding and breast milk
As of the revision date, no relevant published information was found.

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Protein binding rate
85%
Preclinical toxicity studies of carbimazole have established its safety profile. Adverse effects are similar to other thionamide antithyroid agents and include agranulocytosis (a rare but serious side effect), rash, gastrointestinal disturbances, and hepatotoxicity. The compound is contraindicated in patients with a history of agranulocytosis or severe hypersensitivity to thionamides. Regular monitoring of blood counts is recommended during therapy.

[1]. Carbimazole is an inhibitor of protein synthesis and protects from neuronal hypoxic damage in vitro. J Pharmacol Exp Ther. 2013 Dec;347(3):781-93.

[2]. Effects of Dose Level of Anti-thyroid Drug Carbimazole on Thermoregulation and Blood Constituents in Male Rabbits (Oryctolagus cuniculus). Advances in Research, 2014, 2(3), 129–144.

[3]. Nakashima, T. and A. Taurog, Rapid conversion of carbimazole to methimazole in serum; evidence for an enzymatic mechanism. Clin Endocrinol (Oxf), 1979. 10(6): p. 637-48.

Carbimazole belongs to the imidazole class of drugs. Its structure is similar to methimazole, except that the hydrogen atom on the nitrogen atom is replaced with an ethoxycarbonyl derivative. Carbimazole is a prodrug of methimazole and is used to treat hyperthyroidism. It is both a prodrug of methimazole and an antithyroid drug. Carbimazole is a carbamate, belonging to the 1,3-dihydroimidazole-2-thione class of compounds. Carbimazole is an imidazole antithyroid drug. Carbimazole is metabolized to methimazole, which exerts its antithyroid activity. Carbimazole is an imidazole antithyroid drug. Carbimazole is metabolized to methimazole, which exerts its antithyroid activity. Drug Indications Used to treat hyperthyroidism and thyrotoxicosis. It is also used for patient preparation before thyroidectomy. Mechanism of Action Carbimazole is an antithyroid drug that reduces the uptake and concentration of inorganic iodine by the thyroid gland and decreases the production of diiodotyrosine and thyroxine. Once converted to its active form, methimazole, it prevents thyroid peroxidase from coupling with and iodinizing tyrosine residues on thyroglobulin, thereby reducing the production of thyroid hormones T3 and T4.

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Pharmacodynamics
Carbimazole is an ethoxycarbonyl derivative of methimazole. Its antithyroid effect is due to its conversion to methimazole after absorption. It is used to treat hyperthyroidism and thyrotoxicosis.
Carbimazole is an antithyroid agent and prodrug of methimazole used to treat hyperthyroidism (Graves' disease and other forms of thyrotoxicosis). The compound inhibits thyroid peroxidase, blocking the synthesis of thyroid hormones T3 and T4. Carbimazole is rapidly metabolized to methimazole, which is responsible for the antithyroid activity. It is also used to prepare patients for thyroidectomy. Carbimazole is a widely used medication for the management of hyperthyroidism.

C7H10N2O2S

186.229

186.046

22232-54-8

31072

White to off-white solid powder

1.3±0.1 g/cm3

240.4±23.0 °C at 760 mmHg

124°C

99.2±22.6 °C

0.0±0.5 mmHg at 25°C

1.612

0.34

0

3

2

12

240

0

CFOYWRHIYXMDOT-UHFFFAOYSA-N

InChI=1S/C7H10N2O2S/c1-3-11-7(10)9-5-4-8(2)6(9)12/h4-5H,3H2,1-2H3

ethyl 3-methyl-2-sulfanylideneimidazole-1-carboxylate

Neomercazole Neo-Tireol CarbimazoleCarbimazole 3-Methyl-2-thionoimidazoline-1-carboxylic acid ethyl ester

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~536.97 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (13.42 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (13.42 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (13.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)