Dose dependency of propylthiouracil (PTU) uptake by the thyroid gland was investigated in intact, adult male rats after a single intraperitoneal dose of PTU. PTU pharmacokinetics in rat serum, liver and lung were independent of the size of this single dose of PTU. However, in the thyroid gland, PTU concentrations corrected for dose were disproportionately high at low doses. At low PTU doses, a transport mechanism contributes substantially to thyroidal PTU uptake, but at high PTU doses this transport system becomes saturated. Thus, at serum PTU concentrations of 5 μg/ml or above, thyroid to serum (T/S) PTU ratios are independent of PTU dose and serum concentration. Alteration in the functional status of the thyroid changed the relationship between serum and thyroidal PTU concentrations. Thyroxine administration prior to an intraperitoneal PTU dose of 5 mg/kg reduced ratios of T/S PTU concentrations. However, thyrotropic hormone (TSH) preadministration had little effect on early thyroidal PTU concentration, but appeared to exert an effect at later times. Chronic administration of either potassium iodide or phenobarbital prior to PTU increased T/S PTU ratios, again suggesting an effect of TSH on PTU metabolism in the thyroid.
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