Physicochemical Properties
| Molecular Formula | C7H10N2O2S |
| Molecular Weight | 186.229 |
| Exact Mass | 186.046 |
| CAS # | 22232-54-8 |
| PubChem CID | 31072 |
| Appearance | White to off-white solid powder |
| Density | 1.3±0.1 g/cm3 |
| Boiling Point | 240.4±23.0 °C at 760 mmHg |
| Melting Point | 124°C |
| Flash Point | 99.2±22.6 °C |
| Vapour Pressure | 0.0±0.5 mmHg at 25°C |
| Index of Refraction | 1.612 |
| LogP | 0.34 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 3 |
| Rotatable Bond Count | 2 |
| Heavy Atom Count | 12 |
| Complexity | 240 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | CFOYWRHIYXMDOT-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C7H10N2O2S/c1-3-11-7(10)9-5-4-8(2)6(9)12/h4-5H,3H2,1-2H3 |
| Chemical Name | ethyl 3-methyl-2-sulfanylideneimidazole-1-carboxylate |
| Synonyms | Neomercazole Neo-Tireol CarbimazoleCarbimazole 3-Methyl-2-thionoimidazoline-1-carboxylic acid ethyl ester |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation Carbimazole is not approved for marketing in the United States by the U.S. Food and Drug Administration, but is available in other countries. Doses of carbimazole of 30 mg daily or 50 mg weekly have not adversely affected the few breastfed infants studied. Carbimazole is a prodrug for methimazole which has been studied extensively during breastfeeding; maternal methimazole therapy does not affect thyroid function or intellectual development in breastfed infants with doses up to 20 mg daily. Some experts now recommend that methimazole should be considered the antithyroid drug of choice in nursing mothers. The American Thyroid Association recommends only monitoring infants for appropriate growth and development during routine pediatric health and wellness evaluations and routine assessment of serum thyroid function in the child is not recommended. Rare idiosyncratic reactions (e.g., agranulocytosis) might occur, and the infant should be watched for signs of infection. Monitoring of the infant's complete blood count and differential is advisable if there is a suspicion of a drug-induced blood dyscrasia. ◉ Effects in Breastfed Infants Eleven mothers were taking oral carbimazole in dosages ranging from 5 to 20 mg daily during pregnancy and 5 to 15 mg daily during breastfeeding (extent not stated). None of the 12 infants, including one set of twins, had a serum thyroxine (T4) concentration below the lower limit of normal on day 4 of life. Thyrotropin (TSH) concentrations were normal in all infants when measured at various times over the first 21 days postpartum. Four women were receiving 10 to 20 mg of carbimazole daily. Infant blood samples were obtained on days 4, 7, 10, and 42 and at 3 and 6 months postpartum. Thyroid function was normal in 3 infants. In one infant, the TSH was elevated for the first 10 days of life. A mother with twins began taking carbimazole 30 mg daily 2 months postpartum. The dosage was lowered as she became euthyroid. The infants were breastfed (extent not stated) and clinical and laboratory examinations were performed over the following 4 months. There was no evidence of alterations in thyroid function. Fifteen mothers received carbimazole 10 to 20 mg daily for 12 to 40 weeks during pregnancy and 9 continued to take the drug during 2 to 26 weeks of lactation. Their infants were monitored for up to 18 months. Infant thyroid function was within nornml over this period, the range of mean values for individual infants being TSH 1.4 to 5.9 millliunits/L, free T3 6.2 to 9.3 pmol/L and T4 104 to 189 nmol/L. Physical examination at intervals for 2 to 18 months was normal in all infants who received carbimazole and Griffiths mental development scales were normal in all 6 infants who were assessed at 18 months. A mother was taking carbimazole 50 mg once weekly during pregnancy and postpartum. Her infant was exclusively breastfed for the first 84 days of life and had clinical and laboratory examinations performed over the first 4 months of life. Although the infant's tone and deep tendon reflexes were slightly increased and she was easily irritable, serum thyroid hormone levels were normal as was her growth. No symptoms or signs of hypothyroidism were observed. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Protein Binding 85% |
| References |
[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. |
| Additional Infomation |
Carbimazole is a member of the class of imidazoles that is methimazole in which the nitrogen bearing a hydrogen is converted into its ethoxycarbonyl derivative. A prodrug for methimazol, carbimazole is used for the treatment of hyperthyroidism. It has a role as a prodrug and an antithyroid drug. It is a carbamate ester and a member of 1,3-dihydroimidazole-2-thiones. An imidazole antithyroid agent. Carbimazole is metabolized to methimazole, which is responsible for the antithyroid activity. An imidazole antithyroid agent. Carbimazole is metabolized to METHIMAZOLE, which is responsible for the antithyroid activity. Drug Indication For the treatment of hyperthyroidism and thyrotoxicosis. It is also used to prepare patients for thyroidectomy. Mechanism of Action Carbimazole is an aitithyroid agent that decreases the uptake and concentration of inorganic iodine by thyroid, it also reduces the formation of di-iodotyrosine and thyroxine. Once converted to its active form of methimazole, it prevents the thyroid peroxidase enzyme from coupling and iodinating the tyrosine residues on thyroglobulin, hence reducing the production of the thyroid hormones T3 and T4. Pharmacodynamics Carbimazole is a carbethoxy derivative of methimazole. Its antithyroid action is due to its conversion to methimazole after absorption. It is used to treat hyperthyroidism and thyrotoxicosis. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~536.97 mM) |
| Solubility (In Vivo) |
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. 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. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 5.3697 mL | 26.8485 mL | 53.6970 mL | |
| 5 mM | 1.0739 mL | 5.3697 mL | 10.7394 mL | |
| 10 mM | 0.5370 mL | 2.6849 mL | 5.3697 mL |