In human beta cells, methimazole TNF for CXC chemokine ligand 10 [3].

Absorption, Distribution and Excretion
Absorption of methimazole after oral administration is rapid and extensive, with an absolute bioavailability of approximately 0.93 and a Tmax ranging from 0.25 to 4.0 hours. Cmax is slightly, but not significantly, higher in hyperthyroid patients, and both Cmax and AUC are significantly affected by the oral dose administered.
Urinary excretion of unchanged methimazole has been reported to be between 7% and 12%. Elimination via feces appears to be limited, with a cumulative fecal excretion of 3% after administration of methimazole. Enterohepatic circulation also appears to play a role in the elimination of methimazole and its metabolites, as significant amounts of these substances are found in the bile post-administration.
The apparent volume of distribution of methimazole has been reported as roughly 20 L. Following oral administration, methimazole is highly concentrated in the thyroid gland - intrathyroidal methimazole levels are approximately 2 to 5 times higher than peak plasma levels, and remain high for 20 hours after ingestion.
Following a single intravenous bolus injection of 10mg of methimazole, clearance was found to be 5.70 L/h. Renal impairment does not appear to alter clearance of methimazole, but patients with hepatic impairment showed a reduction in clearance roughly proportional to the severity of their impairment - moderate insufficiency resulted in a clearance of 3.49 L/h, while severe insufficiency resulted in a clearance of 0.83 L/h. There does not appear to be any significant differences in clearance based on thyroid status (i.e. no difference between euthyroid and hyperthyroid patients).
FOUR DAYS AFTER IV ADMIN OF (14)C-METHIMAZOLE TO RATS, RETENTION OF (14)C WAS GREATEST IN THYROID & ADRENALS; 76% OF DOSE HAD BEEN EXCRETED IN URINE & 6% IN FECES.
(14)C-METHIMAZOLE RADIOACTIVITY CONCENTRATES MORE IN THE THYROID THAN IN ANY OTHER TISSUE, WITH THYROID:PLASMA RATIO REACHING 62.5 AFTER 4 DAYS' CONTINUOUS DOSING.
COMPLETE ABSORPTION...FROM ORAL DOSES...DEMONSTRATED IN RATS. ...IS NEGLIGIBLY BOUND TO PLASMA PROTEINS &...EXHIBITS SINGLE-COMPARTMENT KINETICS EVEN AFTER IV DOSES. ...ATTRIBUTED TO FASTER TISSUE PENETRATION BY METHIMAZOLE DUE TO ITS HIGHER LIPID:WATER PARTITION COEFFICIENT.
BILIARY EXCRETION OF RADIOACTIVITY FROM...(35)S-METHIMAZOLE...AMOUNTED TO ONLY 21%...OF IV DOSES. BILIARY RADIOACTIVITY WAS ALMOST ENTIRELY DUE TO METABOLITES...
For more Absorption, Distribution and Excretion (Complete) data for METHIMAZOLE (9 total), please visit the HSDB record page.

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Metabolism / Metabolites
Methimazole is rapidly and extensively metabolized by the liver, mainly via the CYP450 and FMO enzyme systems. Several metabolites have been identified, though the specific enzyme isoforms responsible for their formation are not entirely clear. One of the first methimazole metabolites identified, 3-methyl-2-thiohydantoin, may contribute to antithyroid activity - its antithyroid activity has been demonstrated in rats and may explain the prolonged duration of iodination inhibition following administration despite methimazole's relatively short half-life. A number of metabolites have been investigated as being the culprits behind methimazole-induced hepatotoxicity. Both glyoxal and N-methylthiourea have established cytotoxicity and are known metabolic products of methimazole's dihydrodiol intermediate. Sulfenic and sulfinic acid derivatives of methimazole are thought to be the ultimate toxicants responsible for hepatotoxicity, though their origin is unclear - they may arise from direct oxidation of methimazole via FMO, or from oxidation of N-methylthiourea further downstream in the metabolic process.
ADMIN...TO SPRAGUE-DAWLEY RATS...UP TO 21% OF DOSE...EXCRETED UNCHANGED IN 24-HR URINE, IN WHICH MAJOR METABOLITE WAS...GLUCURONIDE (36-48%); REMAINING URINARY METABOLITE HAS NOT BEEN IDENTIFIED.
INCUBATION OF METHIMAZOLE WITH RAT HEPATIC MICROSOMES LED TO FORMATION OF 3-METHYL-2-THIOHYDANTOIN & N-METHYLIMIDAZOLE.

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Biological Half-Life
Following a single intravenous bolus injection of 10mg of methimazole, the t_1/2 of the distribution phase was 0.17 hours and the t_1/2 of the elimination phase was 5.3 hours. Methimazole's primary active metabolite, 3-methyl-2-thiohydantoin, has a half-life approximately 3 times longer than its parent drug. Renal impairment does not appear to alter the half-life of methimazole, but patients with hepatic impairment showed an increase in half-life roughly proportional to the severity of their impairment - moderate insufficiency resulted in a elimination t_1/2 of 7.1 hours, while severe insufficiency resulted in an elimination t_1/2 of 22.1 hours. There does not appear to be any significant differences in half-life based on thyroid status (i.e. no difference between euthyroid and hyperthyroid patients).
Plasma half-life is 3-5 hr
The elimination half-life of methimazole reportedly ranges from about 5-13 hours.
T/2...IN PLASMA...FOR METHIMAZOLE IS ABOUT 4-6 HR. ...

Interactions
...BILIARY EXCRETION WAS INCREASED BY PENTOBARBITAL. ADMIN OF BOTH PROPYLTHIOURACIL & METHIMAZOLE CAUSES INCR SERUM TRI-IODOTHYRONINE (T3):THYROXINE 1(T4) RATIO IN PT, OWING EITHER TO DIRECT ACTION ON THYROID GLAND OR TO INCR PERIPHERAL DEIODINATION OF T4 TO T3.
Hyperthyroid patients have exhibited increased metabolic clearance of aminophylline and theophyline, which returned to normal as the patients became euthyroid; decreased dose of aminophylline, oxtriphylline, or theophylline may be necessary as patients become euthyroid. /Antithyroid agents/
Iodide or iodine excess may decrease response to antithyroid agents, requiring an increase in dosage or longer duration of therapy with antithyroid agents; amiodarone contains 37% iodine by weight, and therefore its use significantly increases iodine intake; iodine deficiency may increase response to antithyroid agents requiring a decrease in dosage or shorter duration of therapy with antithyroid agents. /Antithyroid agents/
As thyroid and metabolic status of patient decreases toward normal, response to oral anticoagulants may decrease; however, if thioamide-induced hypoprothrombinemia occurs, anticoagulant effect may be enhanced; adjustment of oral anticoagulant dosage on the basis of prothrombin time is recommended. /Antithyroid agents/
For more Interactions (Complete) data for METHIMAZOLE (6 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Rat oral 2250 mg/kg
LD50 Rat sc 1050 mg/kg
LD50 Mouse oral 860 mg/kg
LD50 Mouse ip 500 mg/kg
LD50 Mouse sc 345 mg/kg

[1]. Effects of long-term oral administration of methimazole on femur and tibia properties in male Wistar rats. Biomed Pharmacother. 2017 Oct;94:124-128.

[2]. Mechanisms of methimazole cytotoxicity in isolated rat hepatocytes. Drug Chem Toxicol. 2013 Oct;36(4):403-11.

[3]. Methimazole inhibits CXC chemokine ligand 10 secretion in human thyrocytes. J Endocrinol. 2007 Oct;195(1):145-55.

[4]. Comparison of methimazole and propylthiouracil in patients with hyperthyroidism caused by Graves' disease. J Clin Endocrinol Metab. 2007 Jun;92(6):2157-62. Epub 2007 Mar 27.

Therapeutic Uses
Antithyroid Agents
METHIMAZOLE IS APPROX 10 TIMES AS POTENT AS PROPYLTHIOURACIL & IS MORE PROMPT IN ELICITING ANTITHYROID RESPONSE. DRUG ALSO EXHIBITS MORE PROLONGED ACTION THAN PROPYLTHIOURACIL...
...USED IN TREATMENT OF HYPERTHYROIDISM...(1) AS DEFINITIVE TREATMENT, TO CONTROL DISORDER IN ANTICIPATION OF SPONTANEOUS REMISSION IN GRAVE'S DISEASE; (2) IN CONJUNCTION WITH RADIOIODINE, TO HASTEN RECOVERY WHILE AWAITING EFFECTS OF RADIATION; & (3) TO CONTROL DISORDER IN PREPN FOR SURGICAL TREATMENT. /ANTITHYROID DRUGS/
THERE ARE NO COMMERCIAL PREPN AVAIL FOR PARENTERAL USE IN RARE EVENT THAT TREATMENT CANNOT BE GIVEN BY MOUTH. FOR THIS EVENTUALITY & FOR EXPTL PURPOSES, FREELY WATER-SOL COMPD, METHIMAZOLE, CAN BE DISSOLVED IN SALINE SOLN & STERILIZED BY HEAT.
Methimazole /is/ indicated in the treatment of hyperthyroidism, including prior to surgery or radiotherapy, and as adjunct in the treatment of thyrotoxicosis or thyroid storm. Propylthiouracil may be preferred over methimazole for use in thyroid storm, since propylthiouracil inhibits peripheral conversion of thyroxine (T4) to triiodothyronine (T3). /Included in US product labeling/

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Drug Warnings
...WOMEN TAKING THESE AGENTS SHOULD NOT BREAST-FEED THEIR INFANTS. /ANTITHYROID DRUGS/
BECAUSE AGRANULOCYTOSIS CAN DEVELOP RAPIDLY, PERIODIC WHITE-CELL COUNTS ARE OF LITTLE HELP. PATIENTS SHOULD IMMEDIATELY REPORT DEVELOPMENT OF SORE THROAT OR FEVER, WHICH USUALLY HERALDS ONSET OF THIS REACTION.
MAIN DRAWBACK TO THERAPY WITH ANTITHYROID DRUGS IS HIGH INCIDENCE OF RELAPSE WHEN TREATMENT IS STOPPED. ... FREQUENT TAKING OF MEDICATION FOR LONG PERIODS OF TIME IS ANOTHER DISADVANTAGE &, ALTHOUGH UNTOWARD REACTIONS...ARE NOT FREQUENT & RARELY SERIOUS, THEY CONSTITUTE FURTHER DISADVANTAGE.
CROSS SENSITIVITY TO OTHER THIOAMIDE DERIVATIVES MAY OCCUR IN SUSCEPTIBLE PT.
For more Drug Warnings (Complete) data for METHIMAZOLE (13 total), please visit the HSDB record page.

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Pharmacodynamics
Methimazole inhibits the synthesis of thyroid hormones resulting in an alleviation of hyperthyroidism. Onset of action occurs within 12 to 18 hours, and its duration of action is 36 to 72 hours, likely due to concentration of methimazole and some metabolites within the thyroid gland after administration. The most serious potential side effect of methimazole therapy is agranulocytosis, and patients should be instructed to monitor for, and report, any signs or symptoms of agranulocytosis such as fever or sore throat. Other cytopenias may also occur during methimazole therapy. There also exists the potential for severe hepatic toxicity with the use of methimazole, and monitoring for signs and symptoms of hepatic dysfunction, such as jaundice, anorexia, pruritus, and elevation in liver transaminases, is prudent in patients using this therapy.

C4H6N2S

114.1688

114.025

60-56-0

Methimazole-d3;1160932-07-9

1349907

White to off-white solid powder

1.3±0.1 g/cm3

280.0±9.0 °C at 760 mmHg

144-147 °C(lit.)

123.1±18.7 °C

0.0±0.6 mmHg at 25°C

1.633

-0.34

1

1

0

7

119

0

PMRYVIKBURPHAH-UHFFFAOYSA-N

InChI=1S/C4H6N2S/c1-6-3-2-5-4(6)7/h2-3H,1H3,(H,5,7)

3-methyl-1H-imidazole-2-thione

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 (~875.89 mM)
H2O : ≥ 50 mg/mL (~437.94 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (21.90 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 (21.90 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 (21.90 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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Solubility in Formulation 4: 100 mg/mL (875.89 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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