Propylthiouracil

(BAN, rINN)
Propylthiouracil Chemical formula
Synonyms: Proiltiourasil; Propiltiouracil; Propiltiouracilas; Propiltiouracilo; Propylthiouracile; Propylthiouracilum; Propyltiouracil; Propyylitiourasiili. 2,3-Dihydro-6-propyl-2-thioxopyrimidin-4(1H)-one; 2-Mercapto-6-propylpyrimidin-4-ol; 6-Propyl-2-thiouracil.
Cyrillic synonym: Пропилтиоурацил.

💊 Chemical information

Chemical formula: C7H10N2OS = 170.2.
CAS — 51-52-5.
ATC — H03BA02.
ATC Vet — QH03BA02.

Pharmacopoeias.

In Chin., Eur., Int., Jpn, and US.

Ph. Eur. 6.2

(Propylthiouracil). White or almost white crystals or crystalline powder. Very slightly soluble in water; sparingly soluble in alcohol; dissolves in solutions of alkali hydroxides. Protect from light.

USP 31

(Propylthiouracil). A white, powdery, crystalline substance. It is starch-like in appearance and to the touch. Slightly soluble in water, in chloroform, and in ether; sparingly soluble in alcohol; soluble in ammonium hydroxide and in alkali hydroxides. Protect from light.

💊 Adverse Effects and Precautions

As for Carbimazole, although cross-sensitivity to carbimazole does not necessarily occur. Propylthiouracil has been associated with greater hepatotoxicity than other thiourea antithyroid drugs (such as carbimazole or thiamazole). Rarely hepatitis, hepatic necrosis, encephalopathy, and death have occurred; asymptomatic liver damage is more common. Propylthiouracil should be given with care, and in reduced doses, to patients with renal impairment.

Breast feeding.

Propylthiouracil has been preferred to carbimazole or thiamazole since it enters breast milk less readily, see Breast Feeding, under Carbimazole.

💊 Pharmacokinetics

Propylthiouracil is rapidly absorbed from the gastrointestinal tract with a 50 to 75% bioavailability and with peak plasma concentrations occurring about 2 hours after oral doses. It is concentrated in the thyroid gland; since its duration of action is more closely related to the intrathyroidal drug concentration than its plasma halflife, prolonged antithyroid activity results from single daily doses. Propylthiouracil is about 80% bound to plasma proteins. Propylthiouracil has an elimination half-life of about 1 to 2 hours. It undergoes rapid first-pass metabolism in the liver, and is mainly excreted in the urine as the glucuronic acid conjugate, with less than 2% excreted as unchanged drug. The elimination half-life may be increased in renal or hepatic impairment. Propylthiouracil crosses the placenta and is distributed into breast milk.

💊 Uses and Administration

Propylthiouracil is a thiourea antithyroid drug that acts by blocking the production of thyroid hormones; it also inhibits the peripheral deiodination of thyroxine to tri-iodothyronine. It is used in the management of hyperthyroidism, including the treatment of Graves’ disease, preparation of hyperthyroid patients for thyroidectomy, use as an adjunct to radioiodine therapy, and the treatment of thyroid storm. Propylthiouracil is usually given orally. Initial doses range from 150 to 450 mg daily (the BNF recommends 200 to 400 mg daily), although in severe cases initial doses of 600 to 1200 mg daily have been used. It has often been given in divided daily doses but once daily dosage is also possible. Improvement is usually seen in 1 to 3 weeks and control of symptoms is achieved in 1 to 2 months. When the patient is euthyroid the dose is gradually reduced to a maintenance dose, usually 50 to 150 mg daily. Treatment is usually continued for 1 to 2 years. In the UK, the BNFC recommends the following initial doses by mouth for children:
in neonates: 2.5 to 5 mg/kg twice daily
in those aged 1 month to 1 year: 2.5 mg/kg three times daily
in those aged 1 to 5 years: 25 mg three times daily
in those aged 5 to 12 years: 50 mg three times daily
in those aged 12 to 18 years: 100 mg three times daily These doses are given until the patient is euthyroid and then adjusted as needed; higher doses may be required, especially in thyrotoxic crises. Doses should be reduced in renal impairment (below). Doses may also need to be reduced in hepatic impairment.

Administration in renal impairment.

The dosage of propylthiouracil should be reduced in patients with renal impairment according to creatinine clearance (CC) as follows:
CC 10 to 50 mL/minute, doses should be reduced by 25%
CC less than 10 mL/minute, reduce doses by 50%

Alcoholic liver disease.

Propylthiouracil has been said to reduce hyperoxic liver injury in hypermetabolic animals and despite reports of hepatotoxicity, including some fatalities, associated with propylthiouracil, it has been investigated in the treatment of patients with alcoholic liver disease. A systematic review1, however, concluded that there is no evidence to substantiate this use. Propylthiouracil was associated with adverse effects and it could not be shown to have any significant effects on mortality, liver related mortality, liver complications, and liver histology.
1. Rambaldi A, Gluud C. Propylthiouracil for alcoholic liver disease. Available in The Cochrane Database of Systematic Reviews; Issu
4. Chichester: John Wiley; 2005 (accessed 01/08/08).

Psoriasis.

Several reports have described benefit in patients with psoriasis given propylthiouracil. An oral dose of 300 mg daily for 8 to 12 weeks has been used and is said not to produce clinical hypothyroidism.1
1. Elias AN. Anti-thyroid thioureylenes in the treatment of psoriasis. Med Hypotheses 2004; 62: 431–7.

💊 Preparations

BP 2008: Propylthiouracil Tablets; USP 31: Propylthiouracil Tablets.

Proprietary Preparations

Austria: Prothiucil; Braz.: Propil; Propilracil; Canad.: Propyl-Thyracil; Cz.: Propycil; Ger.: Propycil; Thyreostat II†; Gr.: Prothuril; Hong Kong: CPPTU; Hung.: Propycil; Israel: Propylthiocil; Pol.: Thyrosan; Port.: Propycil; Swed.: Tiotil; Switz.: Propycil; Thai.: Propyl; Uracil; Turk.: Propycil.
Published October 29, 2018.