In U-937 cells, propylthiouracil (5.5-330 μg/mL; 24 h) causes cytotoxicity and growth retardation in a dose-dependent manner [2].

Propylthouracil induces hypothyroidism in C57BL/6J mice and wild WSB/EiJ elk by administering an iodine-deficient diet supplemented with 0.15% Propylthouracil [1].

Cell Viability Assay[2]
Cell Types: U-937 cells
Tested Concentrations: 5.5 μg/mL, 11 μg/mL, 110 μg/mL, 220 μg/mL, 330 μg/mL
Incubation Duration: 24 hrs (hours)
Experimental Results: Dose-dependent way to induce cytotoxicity.

Animal/Disease Models: Adult C57BL/6J and wild-type WSB/EiJ male mice (8 weeks old) [1]
Doses: 1.5 g/kg Dietary
Route of Administration: Iodine-deficient diet; continued for 7 weeks
Experimental Results: In adult C57BL/6J and wild-type WSB/EiJ induces hypothyroidism in male mice.

Absorption, Distribution and Excretion
Well absorbed following oral administration.
Propylthiouracil is readily absorbed and is extensively metabolized. Approximately 35% of the drug is excreted in the urine, in intact and conjugated forms, within 24 hours.
Elimination: Less than 1% is excreted in the urine unchanged. Total body clearance is approximately 7 L/hr. In dialysis: Elimination and pharmacokinetics are not significantly altered in hemodialysis. In one patient undergoing hemodialysis, 5% of a 200 mg oral dose was removed by 3 hours of hemodialysis; elimination rate was not significantly altered. Peak serum concentration was decreased (from 7.9 to 4.9 ug/mL), although it remained within an approximate therapeutic range.
Although distribution of propylthiouracil into human body tissues and fluids has not been fully characterized, the drug appears to be concentrated in the thyroid gland. Propylthiouracil readily crosses the placenta. Propylthiouracil is distributed into milk; however, some studies indicate that the extent of distribution is only about 0.007-0.077% of a single dose.
Propylthiouracil is rapidly and readily absorbed from the GI tract following oral administration with peak plasma concentrations of about 6-9 mcg/mL occurring within 1-1.5 hours after a single dose of 200-400 mg. In one study in which the drug was administered orally and IV, about 75% of the oral dose was absorbed. Plasma concentrations of the drug do not appear to correlate with the therapeutic effects.
Time to peak effect: 17 weeks (average) to normalize serum T3 and T4 concentrations with use of 300 mg/day.
For more Absorption, Distribution and Excretion (Complete) data for PROPYL THIOURACIL (19 total), please visit the HSDB record page.

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Metabolism / Metabolites
Propylthiouracil was concentrated by thyroid gland, and four sulfur-35 compounds were demonstrated by TLC in both rat and man: unchanged propylthiouracil, (35)-sulfate, unknown propylthiouracil metabolite and protein-bound sulfur-35...
Biotransformation: Primarily undergoes glucuronidation. Approximately 33% of an orally administered dose is metabolized by a first-pass effect.
Presence of more than one glucuronide conjugate of propylthiouracil ought to be expected, as it has four functional groups, each capable of conjugation with glucuronic acid ...
Although the exact metabolic fate of propylthiouracil has not been fully established, the drug is rapidly metabolized to its glucuronide conjugate and other minor metabolites and requires frequent administration to maintain its antithyroid effect. The drug and its metabolites are excreted in urine, with about 35% of a dose excreted within 24 hours.
For more Metabolism/Metabolites (Complete) data for PROPYL THIOURACIL (8 total), please visit the HSDB record page.
Route of Elimination: Propylthiouracil is readily absorbed and is extensively metabolized. Approximately 35% of the drug is excreted in the urine, in intact and conjugated forms, within 24 hours.
Half Life: 2 hours

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Biological Half-Life
2 hours
The elimination half-life of propylthiouracil has generally been reported to be about 1-2 hours.
The plasma half-life of propylthiouracil .../is/ 1 to 2 hours.
/After GI absorption/ plasma half-lives of 2.5 hr (human) and 4.8 hr (rat) have been reported ... .
The half-life of propylthiouracil in plasma is about 75 min ...
Propylthiouracil is rapidly absorbed from /orally/ dosed tablets in man, yielding max plasma levels at 60-120 min, and biological t/2 of about 60 min in euthyroid subjects.

Toxicity Summary
Propylthiouracil binds to thyroid peroxidase and thereby inhibits the conversion of iodide to iodine. Thyroid peroxidase normally converts iodide to iodine (via hydrogen peroxide as a cofactor) and also catalyzes the incorporation of the resulting iodide molecule onto both the 3 and/or 5 positions of the phenol rings of tyrosines found in thyroglobulin. Thyroglobulin is degraded to produce thyroxine (T4) and tri-iodothyronine (T3), which are the main hormones produced by the thyroid gland. Therefore propylthiouracil effectively inhibits the production of new thyroid hormones.

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Toxicity Data
Oral, rat: LD₅₀ = 1250 mg/kg.

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Interactions
In addition to blocking hormone synthesis, propylthiouracil inhibits the peripheral deiodination of thyroxine to triiodothyronine. Methimazole dose not have this effect and can antagonize the inhibitory effect of propylthiouracil.
We have investigated immunohistochemically the effect of dl-alpha-tocopherol (vitamin E) on thyroid gland with 6-n-propyl-2-thiouracil (PTU)-induced hypothyroidism in rats. The animals were divided into four groups. Rats in group I were designated as control, rats in group II were treated with injections of PTU (10 mg/kg) for 15 days, rats in group III were treated with injections of PTU+vitamin E (10 mg/100 g) for 15 days. Rats in group IV were treated with injections PTU for 15 days and kept for 15 next days after cessation of PTU treatment. At the end of experiment, the animals were killed by decapitation, blood samples were obtained, thyroid tissues were collected and processed for quantitative evaluation of immunohistochemical PCNA (marker of cell proliferation), Bax (pro-apoptotic marker) and Bcl-2 (anti-apoptotic marker) staining. There was an increase in the number of PCNA-immunopositive cells in follicular epithelial cells of group II rats compared with other groups (p<0.05). After vitamin E treatment, the number of PCNA-immunopositive cells decreased (p<0.05) while the number of Bax-immunopositive cells increased (p<0.05). The number of Bcl-2-positive follicular epithelial cells of group IV rats was higher than in those of other groups (p<0.05). The results of this study indicate that hypothyroidism induces cell proliferation in the thyroid gland and vitamin E may promote involution of the gland.
Female Sprague-Dawley rats, 50-60 days of age, were given 7,12-dimethylbenz[ a]anthracene (DMBA) in sesame oil by oral gavage at a dose of 6.5, 10, 13.5 or 15 mg per animal. Propylthiouracil was given in the drinking-water at concentrations between 0.5 and 4.0 mg/100 mL for various times before and after the DMBA treatment, ranging from 17 days before DMBA up to the end of the study at 4 months. Severe hypothyroidism produced by administration of propylthiouracil at the higher dose from 7 days before DMBA up to study termination reduced the mammary tumor incidence from 68/108 in rats given DMBA only to 3/45 in those given DMBA plus propylthiouracil.
Two groups of 21 male inbred Wistar rats, 6 weeks of age, were fed basal diet containing propylthiouracil [purity not specified] at a concentration of 0.15% either alone or in combination with a single intraperitoneal injection of N-nitrosobis(2- hydroxypropyl)amine (NBHPA) at the start of the study at a dose of 2.8 g/kg bw. Two additional groups received the initiating dose of NBHPA alone or basal diet alone (control group). The animals were maintained for 20 weeks, at which time the survival rate was 100%. Thyroid follicular-cell tumors occurred in 21/21 rats given NBHPA plus propylthiouracil, 4/21 given NBHPA only (p<0.05) and 0/21 given propylthiouracil only or no treatment. Of the rats given NBHPA plus propylthiouracil, seven of those bearing thyroid tumors had thyroid carcinomas.
For more Interactions (Complete) data for PROPYL THIOURACIL (7 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Rat oral 1980 mg/kg

[1]. A Fine Regulation of the Hippocampal Thyroid Signalling Protects Hypothyroid Mice against Glial Cell Activation. Int J Mol Sci. 2022 Oct 8;23(19):11938.

[2]. Synergistic effect of phospholipid-based liposomes and propylthiouracil on U-937 cell growth. J Liposome Res. 2005;15(3-4):215-27.

Therapeutic Uses
Mesh Heading: Antimetabolites, Antithyroid Agents
... Propylthiouracil /is/ indicated in the treatment of hyperthyroidism, including prior to surgery or radiotherapy, and as adjuncts 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).
EXPTL USE: Paradoxically propylthiouracil has been shown to reverse histological changes of alcoholic hepatitis in rat and has been proposed as possible treatment for this condition in man.
EXPTL USE: Twelve-day pretreatment with PTU prevented the tylenol-induced increase in transaminase activities. Increase in hepatic reduced glutathione levels and prevention of inflammatory response to necrotic liver tissue appeared to be mechanism in protective action of hypothyroidism.
For more Therapeutic Uses (Complete) data for PROPYL THIOURACIL (14 total), please visit the HSDB record page.

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Drug Warnings
Although reported much less frequently, severe adverse effects, including inhibition of myelopoiesis with resultant agranulocytosis, granulocytopenia, and thrombocytopenia; aplastic anemia; drug fever; lupus-like syndrome (including splenomegaly); severe hepatic reactions (including encephalopathy, fulminant hepatic necrosis, and death); periarteritis; and hypoprothrombinemia and bleeding, have been reported to occur in some patients receiving propylthiouracil. Nephritis and interstitial pneumonitis have also been reported. Cutaneous vasculitis, which may manifest as purpuric and/or bullous hemorrhagic lesions or erythema nodosum, and possibly may progress to necrotic ulcerations, and polymyositis also have occurred.
Agranulocytosis is potentially the most serious adverse effect of propylthiouracil, and most cases of agranulocytosis appear to occur within the first 2 months of therapy, but rarely may occur after 4 months of therapy. The risk of propylthiouracil-induced agranulocytosis appears to be substantially increased in patients older than 40 years of age compared with younger patients, but, unlike methimazole, an association with dosage has not been established. Although the mechanism(s) of propylthiouracil-induced agranulocytosis has not been determined, antigranulocyte antibodies have been reported in some patients with thioamide-induced agranulocytosis; a direct toxic effect of these drugs on bone marrow has not been excluded as an additional possible cause.
Propylthiouracil crosses the placenta and may cause fetal harm when administered to pregnant women; the drug can induce goiter and hypothyroidism (cretinism) in the developing fetus. If the drug is used during pregnancy for the management of hyperthyroidism, the manufacturer states that careful dosage adjustment, using a sufficient but not excessive dosage of propylthiouracil, is necessary. The manufacturer states that because thyroid dysfunction diminishes in many women as pregnancy proceeds, a reduction in dosage may be possible, and, in some patients, propylthiouracil can be discontinued 2 or 3 weeks before delivery. If propylthiouracil is used during pregnancy, or if a woman becomes pregnant while receiving the drug, she should be advised of the potential hazard to the fetus.
... Disagreement about therapy of thyrotoxicosis during pregnancy. Antithyroid drugs cross placenta and can cause fetal hypothyroidism and goiter. ... There are 3 choices of therapy, each with its advocates: minimal doses of antithyroid drugs, full doses ... with thyroid hormone supplementation, or surgery. /Antithyroid drugs/
For more Drug Warnings (Complete) data for PROPYL THIOURACIL (20 total), please visit the HSDB record page.

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Pharmacodynamics
Propylthiouracil is a thiourea antithyroid agent. Grave's disease is the most common cause of hyperthyroidism. It is an autoimmune disease where an individual's own antibodies attach to thyroid stimulating hormone receptors within cells of the thyroid gland and then trigger overproduction of thyroid hormone. The two thyroid hormones manufactured by the thyroid gland, thyroxine (T4) and triiodothyronine (T3), are formed by combining iodine and a protein called thyroglobulin with the assistance of an enzyme called peroxidase. PTU inhibits iodine and peroxidase from their normal interactions with thyroglobulin to form T4 and T3. This action decreases thyroid hormone production. PTU also interferes with the conversion of T4 to T3, and, since T3 is more potent than T4, this also reduces the activity of thyroid hormones. The actions and use of propylthiouracil are similar to those of methimazole.

C7H5D5N2OS

175.26

170.051

51-52-5

Propylthiouracil-d5;1189423-94-6

657298

White to off-white solid powder

1.2±0.1 g/cm3

355.2±34.0 °C at 760 mmHg

218-220 °C(lit.)

168.6±25.7 °C

0.0±0.8 mmHg at 25°C

1.601

-0.32

2

2

2

11

223

0

KNAHARQHSZJURB-UHFFFAOYSA-N

InChI=1S/C7H10N2OS/c1-2-3-5-4-6(10)9-7(11)8-5/h4H,2-3H2,1H3,(H2,8,9,10,11)

6-propyl-2-sulfanylidene-1H-pyrimidin-4-one

Procasil-d5; Propylthiouracil-d5; Propylthiouracil

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 (~587.44 mM)
H2O : ~0.67 mg/mL (~3.94 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (14.69 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 (14.69 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 (14.69 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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 (Please use freshly prepared in vivo formulations for optimal results.)