Propylthiouracil

About: Propylthiouracil is a research topic. Over the lifetime, 2181 publications have been published within this topic receiving 46996 citations. The topic is also known as: Thyreostat® & 2,3-dihydro-6-propyl-2-thioxo-4(1H)-pyrimidinone.

Comparison of standardized initial doses of two antithyroid drugs in the treatment of Graves' disease.

Abstract: Objectives. To obtain a simple standard regimen, suitable for general practice, and based upon the addition of antithyroid drug plus thyroxine for attaining euthyroidism in patients with Graves' disease. Design. Prospective, randomized trial of patients with Graves' disease followed for 3 months after the initiation of therapy with an antithyroid drug and combined with the later addition of triiodothyronine to keep the patient euthyroid. The patients were randomized, according to birth date, between methimazole and propylthiouracil. Three dose schemes were tested for each antithyroid drug. Setting. The study was performed at the thyroid outpatient units of two general hospitals, with the patients having been referred from primary care. Subjects. Ninety-four patients with Graves' disease who were suitable for treatment with antithyroid drugs. Interventions. The patients were allocated into six groups. Three groups received methimazole (10 mg every 6th, 8th or 12th h) and three received propylthiouracil (100 mg every 6th, 8th or 12th h). Twenty micrograms of triiodothyronine was added when the patients were euthyroid to avoid hypothyroidism. Main outcome measures. The lowest serum free thyroxine level within 3 months of the initiation of the antithyroid treatment. Results. Fourteen per cent of the patients on methimazole 10 mg every 12th h and 29% on propylthiouracil 100 mg every 12th h did not achieve euthyroidism within the 3-month observation period. All but one patient on methimazole 10 mg every 8th h or propylthiouracil 100 mg every 8th h reduced the free serum thyroxine levels to the normal or hypothyroid range within the observation period. All of the patients on methimazole 10 mg every 6th h and 56% on propylthiouracil 100 mg every 6th h reduced the serum T4 values into the hypothyroid range within the period. Conclusion. A standard regimen, based upon the addition of methimazole 10 mg every 8th or 6th h or propylthiouracil 100 mg every 8th or 6th h and followed by the addition of thyroxine or triiodothyronine when euthyroid to avoid hypothyroidism, seems to be suitable for attaining euthyroidism within 3 months in patients with Graves' disease. A dose scheme based on methimazole 10 mg every 12th h or propylthiouracil 100 mg every 12th h were found to be unsuitable due to an unacceptably high incidence of failure to attain euthyroidism or hypothyroidism within 3 months.

Hepatitis and Propylthiouracil

Abstract: Excerpt Drugs of the thioamide type, introduced during the 1940s for the treatment of thyrotoxicosis, were occasionally noted to produce jaundice. This effect was noted mostly with thiouracil, meth...

Propylthiouracil: absorption, metabolism and excretion in the albino rat

Abstract: 6- n -Propyl-2-thiouracil-6-14C was administered to Sprague-Dawley rats of either sex i.v., i.p. or p.o. at a dose of 20 mg/kg. Sustained plasma levels of radioactivity resulted after i.p. and p.o. doses. Equilibrium dialysis indicated that 57% of the drug in the plasma was protein bound. The drug had no particular affinity for any tissue. Propylthiouracil was found to have low aqueous solubility and chloroform/water partition coefficients. Between 75 and 90% of the administered radioactivity was excreted in the urine and approximately 15% appeared in the bile. Since negligible radioactivity appeared in the feces, the drug was completely absorbed and an enterohepatic circulation was present. The half-life of urinary excretion of radioactivity was four to six hours regardless of the route of administration. Only 9 to 15% of the administered dose was excreted as unchanged drug in the 24-hour urine. The major urinary metabolite was propylthiouracil glucuronide, which accounted for 40 to 48% of the administered dose in 24-hour urine samples. The other urinary metabolite, which accounted for 10 to 16% of the administered dose in 24 hours, has not yet been completely characterized. The major biliary metabolite was determined to be a glucuronide conjugate of propylthiouracil but different from the major urinary metabolite.

Effects of inhibition of type I iodothyronine deiodinase and phenol sulfotransferase on the biliary clearance of triiodothyronine in rats.

Abstract: Recent studies using isolated rat hepatocytes have indicated that the bioactive form of thyroid hormone, T3, is metabolized in liver predominantly by conjugation with glucuronic acid or sulfate. In contrast to T3 itself and the stable glucuronide, T3 sulfate is rapidly degraded by successive deiodination of the tyrosyl and phenolic rings. In the present study we have investigated the biliary excretion of T3 metabolites in male Wistar rats under pentobarbital anesthesia. The animals were injected iv with 1) saline, 2) the deiodinase inhibitor propylthiouracil (PTU; 1 mg/100 g BW), 3) the phenol sulfotransferase inhibitor dichloronitrophenol (2.6 mumol/100 g BW), or 4) a combination of both drugs. After 15 min, 10 muCi [125I]T3 were administered iv, and bile was collected for 30-min periods until 4 h after tracer injection. Secretory products were analyzed by HPLC. In control animals, 22.4% of the dose was excreted in bile mainly in the form of T3 glucuronide. In PTU-treated rats biliary excretion was increased to 36.0% of the dose (P less than .001) due to a dramatic increase in the sulfates of T3 and 3,3'-diiodothyronine. Dichloronitrophenol by itself had no effect on the biliary clearance of T3, but greatly inhibited PTU-induced excretion of sulfates. These results strongly suggest that sulfation and subsequent deiodination is an important pathway of T3 metabolism in vivo.

Accumulation of plasma triiodothyronine sulfate in rats treated with propylthiouracil.

Abstract: Triiodothyronine sulfate (T3S) is rapidly deiodinated by the propylthiouracil (PTU)-sensitive type I deiodinase. Here we examined the effects of PTU on plasma T3S levels in rats after intravenous administration of radiolabeled T3 or T3S. Sephadex LH-20 chromatography and high-performance liquid chromatography were used to quantify conjugated and nonconjugated iodothyronines, and iodide was measured as the TCA-soluble radioactivity. In control rats, radioiodide was the main metabolite of both T3 and T3S. Plasma T3S was cleared more rapidly than plasma T3 despite increased binding to plasma proteins. PTU reduced plasma iodide levels by 66 and 78% after T3 and T3S, respectively, and decreased plasma clearance of T3S by 81%. However, PTU had no effect on plasma T3 clearance but increased plasma T3S from injected T3 4.2 times. Biliary excretion of injected T3S was less than 20% in normal rats, in contrast to 70% within 4 h in PTU-treated rats. In conclusion, T3S is an important intermediate in the in vivo metabolism of T3 in rats and accumulates in plasma if type I deiodination is inhibited.