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Propylthiouracil chemical structure

IUPAC name
CAS number
ATC code


Chemical formula {{{chemical_formula}}}
Molecular weight 170.233 g/mol
Bioavailability 80%-95%
Metabolism ?
Elimination half-life 2 hours
Excretion ?
Pregnancy category D
Legal status Rx
Routes of administration Oral

Propylthiouracil (PTU) or 6-n-propylthiouracil[1] (PROP) is a thiouracil-derived drug used to treat hyperthyroidism (including Graves' disease) by decreasing the amount of thyroid hormone produced by the thyroid gland.[2] Its notable side effects include a risk of agranulocytosis.

On 3 June 2009, the FDA published an alert "notifying healthcare professionals of the risk of serious liver injury, including liver failure and death, with the use of propylthiouracil."[3] As a result, propylthiouracil is no longer recommended in non-pregnant adults and in children as the front line antithyroid medication.[4]


It was approved by the US Food and Drug Administration in 1947.

Mechanism of action


PTU inhibits the enzyme thyroperoxidase, which normally acts in thyroid hormone synthesis by oxidizing the anion iodide (I-) to iodine (I0), facilitating iodine's addition to tyrosine residues on the hormone precursor thyroglobulin. This is one of the essential steps in the formation of thyroxine (T4).[5]

PTU does not inhibit the action of the sodium-dependent iodide transporter located on follicular cells' basolateral membranes. Inhibition of this step requires competitive inhibitors, such as perchlorate and thiocyanate.


PTU also acts by inhibiting the enzyme 5'-deiodinase (tetraiodothyronine 5' deiodinase), which converts T4 to the active form T3. (This is in contrast to methimazole, which shares propylthiouracil's central mechanism, but not its peripheral one.)


Administration is oral, with peak serum concentrations occurring in one hour, and actively concentrated to the thyroid gland. Depending on several patient variables, however, euthyroid status may not be achieved until 2–4 months after treatment initiation. Of note, the drug is approximately 70% protein-bound and significantly ionized at normal physiologic pH, while the antithyroid agent methimazole is substantially less protein bound. However both are equally transferred across the placenta.[6]

The plasma half-life is one hour and is not altered appreciably by the thyroid status of the patient. Due to the concentration in the thyroid, however, dosing intervals may last 8 hours or longer. Less than 10% of the drug is excreted unchanged, with the remaining fraction undergoing extensive hepatic metabolism via glucuronidation.

Side effects

One possible side effect is agranulocytosis,[7] a decrease of white blood cells in the blood. Symptoms and signs of agranulocytosis include infectious lesions of the throat, the gastrointestinal tract, and skin with an overall feeling of illness and fever. A decrease in blood platelets (thrombocytopenia) also may occur. Since platelets are important for the clotting of blood, thrombocytopenia may lead to problems with excessive bleeding. Side effects are suspected and the drug is sometimes discontinued if the patient complains of recurrent episodes of sore throat.

A more life threatening side effect is sudden, severe, fulminant hepatic failure resulting in death or liver transplantation, which occurs in up to 1 in 10,000 people taking propylthiouracil. Unlike agranulocytosis which most commonly occurs in the first three months of therapy, this side effect may occur at any time during treatment.[4]

Propylthiouracil is generally well tolerated, with side effects occurring in one of every 100 patients.[citation needed] The most common side effects are related to the skin, and include rash, itching, hives, abnormal hair loss, and skin pigmentation.[citation needed] Other common side effects are swelling, nausea, vomiting, heartburn, loss of taste, joint or muscle aches, numbness and headache, allergic reactions, and hair whitening.[citation needed]

Propylthiouracil in pregnancy

Propylthiouracil is classified as Drug Class D in pregnancy. Class D signifies there is positive evidence of human fetal risk. Maternal benefit may outweigh fetal risk in life-threatening situations.[8] PTU is preferred over methimazole (which is also a class D) only in the first trimester of pregnancy and in woman who may become pregnant. In the second and third trimester, methimazole is preferred.[4]

The primary effect on the fetus from transplacental passage of PTU is the production of a mild hypothyroidism when the drug is used close to term. This usually resolves within a few days without treatment. The hypothyroid state may be observed as a goiter in the newborn, and is the result of increased levels of fetal pituitary thyrotropin. The incidence of fetal goiter after PTU treatment in reported cases is approximately 12%.[9]

Chemical synthesis

Propylthiouracil can be prepared from ethyl 3-oxohexanoate and thiourea.[10]

File:Propylthiouracil rxn.png


Danielle Reed studies on the genetics of bitter taste perception led to identification of a critical region of human Chromosome 5p15 whose variation correlated with a person's ability to taste the bitterness of PROP (propylthiouracil). This finding ultimately led to the discovery by Adler and co-workers (Charles Zuker) of a family of bitter taste receptors (taste receptor) located within this critical region of the chromosome.

See also


  1. The letter "n" should be a lower case letter, as it describes the nature of the propyl substituent as normal, rather than its position on one of the ring nitrogens. Thereby, the position already is marked by the "6".
  2. Nakamura H, Noh JY, Itoh K, Fukata S, Miyauchi A, Hamada N (June 2007). Comparison of methimazole and propylthiouracil in patients with hyperthyroidism caused by Graves' disease. The Journal of Clinical Endocrinology and Metabolism 92 (6): 2157–62.
  3. Propylthiouracil (PTU)-Induced Liver Failure. FDA. URL accessed on 2009-05-03.
  4. 4.0 4.1 4.2 Bahn RS, Burch HS, Cooper DS, et al. (July 2009). The Role of Propylthiouracil in the Management of Graves' Disease in Adults: report of a meeting jointly sponsored by the American Thyroid Association and the Food and Drug Administration. Thyroid 19 (7): 673–4.
  5. Boron, WF & Boulpaep, EL. 2005. Medical Physiology, Updated Edition. Elsevier Saunders, Philadelphia, PA
  6. Abalovich M, Amino N, Barbour LA, et al. (August 2007). Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society Clinical Practice Guideline. J. Clin. Endocrinol. Metab. 92 (8 Suppl): S1–47.
  7. Cho YY, Shon HS, Yoon HD (December 2005). Management of a pregnant patient with Graves' disease complicated by propylthiouracil induced agranulocytosis. The Korean journal of internal medicine 20 (4): 335–8.
  8. propylthiouracil
  9. Propylthiouracil: Drug safety during pregnancy and breastfeeding / DRUGSAFETYSITE.COM
  10. (1945). Studies in Chemotherapy. X. Antithyroid Compounds. Synthesis of 5- and 6- Substituted 2-Thiouracils from β-Oxoesters and Thiourea. Journal of the American Chemical Society 67 (12).

External links

Template:Thyroid therapy

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