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Research ArticleArticle

PROPYLTHIOURACIL: ABSORPTION, METABOLISM AND EXCRETION IN THE ALBINO RAT

D. S. SITAR and D. P. THORNHILL
Journal of Pharmacology and Experimental Therapeutics November 1972, 183 (2) 440-448;
D. S. SITAR
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D. P. THORNHILL
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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.

Footnotes

    • Received June 24, 1971.
    • Accepted June 23, 1972.
  • © 1972 by The Williams & Wilkins Co.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 183, Issue 2
1 Nov 1972
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Research ArticleArticle

PROPYLTHIOURACIL: ABSORPTION, METABOLISM AND EXCRETION IN THE ALBINO RAT

D. S. SITAR and D. P. THORNHILL
Journal of Pharmacology and Experimental Therapeutics November 1, 1972, 183 (2) 440-448;

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Research ArticleArticle

PROPYLTHIOURACIL: ABSORPTION, METABOLISM AND EXCRETION IN THE ALBINO RAT

D. S. SITAR and D. P. THORNHILL
Journal of Pharmacology and Experimental Therapeutics November 1, 1972, 183 (2) 440-448;
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