Propylthiouracil, with chemical name of 6-propyl-2-thiouracil, is an organic compound with chemical formula of CsevenHtenNtwoOS，It can inhibit the synthesis of thyroid hormone by inhibiting the thyroid peroxidase system, preventing the iodization of tyrosine in thyroid and the condensation of iodized tyrosine.High dose (700mg per day) can reduce the transformation of T4 to T3 in surrounding tissues.This product also has immunosuppressive effect.As this product only inhibits the synthesis of thyroid hormone, it has no effect on the synthesized thyroid hormone, so it will take 3 to 4 weeks for the treatment of hyperthyroidism to show its efficacy.
On October 27, 2017, the list of carcinogens published by the International Agency for Research on Cancer of the World Health Organization (WHO) was preliminarily sorted out for reference, and propylthiouracil was included in the list of Class 2B carcinogens.[1]
Drug name
Propylthiouracil
Foreign name
propylthiouracil[4]、PTU
Mainly applicable
Adult hyperthyroidism
Usage and dosage
Generally 300mg per day
Adverse reactions
Skin rash or itching, abnormal blood system
chemical formula
CsevenHtenNtwoOS
molecular weight
one hundred and seventy point two three two
CAS registration
51-52-5
Science popularization in China
Committed to authoritative science communication
The certification expert of this term is
Zhang Zheng|Pharmacist in charge
Pharmacy Department of Beijing Chaoyang Hospitalto examine
Qiu Kui|Pharmacist in charge
Pharmacy Department of Beijing Chaoyang Hospitalto examine
Solubility: very slightly soluble in water, slightly soluble in ethanol, ether, chloroform, easily soluble in ammonia test solution and sodium hydroxide solution[2]
Molecular structure data
Molar refractive index: 46.67
Molar volume (cmthree/mol）：136.2
Isotonic specific volume (90.2K): 375.4
Surface tension (dyne/cm): 57.6
Polarization (10-24cmthree）：18.50[2]
Calculate chemical data
Reference value for drainage parameter calculation (XlogP): 0.8
Number of hydrogen bond donors: 2
Number of hydrogen bond receptors: 2
Number of rotatable chemical bonds: 2
Number of tautomers: 17
Topological molecular polar surface area: 73.2
Number of heavy atoms: 11
Surface charge: 0
Complexity: 223
Number of isotope atoms: 0
Determine the number of atomic structure centers: 0
Number of uncertain atomic structure centers: 0
Determine the number of chemical bond structure centers: 0
Number of uncertain chemical bond structure centers: 0
Number of covalent bond units: 1[2]
Brief Introduction to Drugs
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Indications
1. Medical treatment of hyperthyroidism
It is applicable to mild illness and those who are not suitable for surgery or radioactive iodine treatment, such as children, adolescents and those who relapse after surgery and are not suitable for radioactive iodine treatment.It can also be used as an auxiliary treatment for radioactive iodine therapy.
2. Treatment of thyroid crisis
In addition to the use of large doses of iodine and other comprehensive measures, a large amount of this product can be used as an auxiliary treatment to block the synthesis of thyroxine.
3. Preoperative preparation
In order to reduce anesthesia and postoperative complications and prevent thyroid crisis after operation, this product should be taken before operation to make thyroid function return to normal or close to normal, and then iodine should be taken about two weeks before operation.
clinical application
1. Adult hyperthyroidism
The commonly used oral dose is 0.05-0.1g once and 0.15-0.3g a day;Extreme amount: 0.2g once, 0.6g daily.After the symptoms are relieved, the maintenance dose of 25-100mg for 1 day is used instead.The starting dose for children is 4 mg/kg per day, taken orally in batches, and the maintenance dose is reduced;
2. Thyroid crisis
0.4~0.8g a day, divided into 3~4 times, and the course of treatment should not exceed 1 week as one of the comprehensive treatment measures;
3. Preoperative preparation for hyperthyroidism
Before operation, take this product to make thyroid function return to normal or near normal, and then take iodine for two weeks before operation.
Adverse reactions
1. Most of the adverse reactions occurred in the first two months of drug use, with skin itching and rash more common. The drug can be stopped or reduced or replaced with other preparations.
2. The serious adverse reactions are abnormal blood system, mild leukopenia, severe agranulocytosis, and aplastic anemia. Therefore, blood picture should be checked regularly after treatment.The rare adverse reaction is hepatitis, which may cause jaundice. The liver function should be checked regularly.Patients with abnormal liver function should use it with caution.Propylthiouracil is more related to hepatotoxicity than other thiourea drugs. Asymptomatic liver damage is more common, such as liver enzyme elevation, but severe reactions such as hepatitis and liver necrosis are rare.The dosage should be reduced for patients with renal insufficiency.
3. Other adverse reactions included gastrointestinal reaction, arthralgia, headache, vasculitis and lupus erythematosus like syndrome;Rare adverse reactions include interstitial pneumonia, nephritis and vasculitis.
matters needing attention
The number of white blood cells in peripheral blood is low;Hypersensitivity to thiourea drugs;Patients with abnormal liver function should use it with caution.If there are symptoms and signs of agranulocytosis or hepatitis, the drug should be stopped.The serious side effect is abnormal blood system. Therefore, blood picture should be checked regularly after treatment.
Drug contraindication
It is forbidden for those allergic to this product.It is forbidden for pregnant and lactating women, nodular goiter with hyperthyroidism, and thyroid cancer patients.
Drug interaction
1. When used in combination with drugs that can inhibit thyroid function and cause goiter, attention should be paid to such drugs as sulfonamides, betamethasone, barbiturates, and sulfonylureas.
2. Avoid taking iodine before using this product.
3. The effect of anticoagulant is reduced.
Note: The above contents are only for introduction. Drug use must be carried out by regular hospitals under the guidance of doctors.
Pharmacopoeia information
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essential information
This product is 6-propyl-2-thio-2,3-dihydro-40（H）Pyrimidone, calculated as dry product, containing CsevenHtenNtwoOS shall not be less than 98.0%.
character
This product is white or almost white crystal or crystalline powder, odorless.
This product is slightly soluble in ethanol, very slightly soluble in water, and dissolved in sodium hydroxide test solution or ammonia test solution.
melting point
The melting point of this product (general rule 0612) is 218-221 ℃.
identify
1. Take the saturated aqueous solution of the product, heat it to boiling, and add the same amount of the newly prepared mixed solution containing 0.4% sodium nitrite cyanide, 0.4% hydroxylamine hydrochloride and 0.8% sodium carbonate, which will turn green and blue.
2. Take about 25mg of this product, drop bromine test solution until it is completely dissolved, heat it, fade it, cool it, drop barium hydroxide test solution to generate white precipitate.
3. The infrared absorption spectrum of this product should be consistent with the control spectrum (spectrum set 70 figure).
4. Take an appropriate amount of this product and propylthiouracil reference, add an appropriate amount of methanol to dissolve them, dilute with water to prepare a solution containing about 25 µ g per 1mL as the test solution and the reference solution.Test according to the method under the item of related substances. In the recorded chromatogram, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the reference solution.
inspect
Thiourea
Determine according to the method of high performance liquid chromatography (general rule 0512).
Test solution: Take about 50mg of this product and place it in a 100mL measuring flask. Add an appropriate amount of mobile phase to dissolve it and dilute it to the scale. Shake it up. Accurately measure 10mL and place it in a 50mL thiourea measuring flask. Dilute it to the scale with mobile phase and shake it up.
Reference solution: Take an appropriate amount of thiourea reference, weigh it precisely, add an appropriate amount of mobile phase to dissolve it and dilute it quantitatively to prepare a solution containing about 0.1 µ g per 1mL.
Chromatographic conditions: octadecyl silane bonded silica gel is used as the filler, water acetonitrile (60:40) is used as the mobile phase, the flow rate is 0.5mL per minute, the detection wavelength is 238nm, and the injection volume is 20 µ L.
System applicability requirements: the resolution of thiourea peak and adjacent peak shall meet the requirements.
Determination method: Precisely measure the test solution and the reference solution, respectively inject them into the liquid chromatograph, and record the chromatogram.
Limit: If there is a chromatographic peak in the chromatogram of the test solution that is consistent with the retention time of thiourea, the peak area shall not exceed 0% according to the external standard method.
Related substances
Determine according to the method of high performance liquid chromatography (general rule 0512).
Test solution: take about 50mg of this product, place it in a 100mL volumetric flask, add 5mL of methanol, shake it for 10 minutes, add 50mL of water, shake it for 20 minutes, dilute it with water to the scale, shake it well, filter it, take 10mL of continued filtrate, place it in a 50mL volumetric flask, dilute it with water to the scale, shake it well.
Reference solution: precisely measure 1mL of the test solution, place it in a 100mL volumetric flask, dilute it with water to the scale, and shake it up.
Chromatographic conditions: octadecyl silane bonded silica gel is used as the filler, 0.02mol/L phosphate buffer solution (3.40g of potassium dihydrogen phosphate, 500mL of water is added to dissolve, phosphoric acid or 0.1mol/L sodium hydroxide solution is used to adjust the pH value to 4.6, and water is added to dilute to 1000mL) - acetonitrile (70:30) is used as the mobile phase, the detection wavelength is 273nm, and the injection volume is 20 μ L.
System applicability requirements: the number of theoretical plates shall not be less than 2000 based on the peak of propylthiouracil, and the separation between the main peak and the adjacent impurity peak shall meet the requirements.
Determination method: Precisely take the test solution and the reference solution, inject them into the liquid chromatograph respectively, and record the retention time of the chromatogram to three times of the main component peak.
Limit: If there are impurity peaks in the chromatogram of the test solution, the sum of the peak areas of each impurity shall not be greater than 1.5 times (1.5%) of the main peak area of the reference solution.
Loss on drying
Take this product, dry it at 105 ℃ to constant weight, and the weight loss shall not exceed 0.5% (general rule 0831).
Ignition residue
Take 1.0g of this product and check it according to the law (general rule 0841). The residual residue shall not exceed 0.1%.
heavy metal
Take the residue left under the item of burning residue and check it according to law (the second method of General Rule 0821). The content of heavy metals shall not exceed 20 parts per million.
Assay
Take about 0.3g of this product, weigh it accurately, add 30mL of water, use a buret to add 30mL of sodium hydroxide titrant (0.1mol/L), boil it and shake it for dissolution, add 50mL of 0.1mol/L silver nitrate solution, continue to heat it and keep it slightly boiling for about 7 minutes, cool it down, titrate it with sodium hydroxide titrant (0.1mol/L) according to the potentiometric titration method (general rule 0701).Every 1mL of sodium hydroxide titrant (0.1mol/L is equivalent to 8.512mg of CsevenHtenNtwoOS。
category
Antithyroid.
Storage
Shading, sealed storage.
preparation
1. Propylthiouracil.
2. Propylthiouracil enteric coated tablets.[3]
security information
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Safety terminology
S36/37：Wear suitable protective clothing and gloves.
Wear appropriate protective clothing and gloves.
S45：In case of accident or if you feel unwell, seek medical advice immediately (show the lable where possible).
In case of an accident or feeling unwell, seek medical advice immediately (show the label if possible).
