UNUSUAL CHARACTERISTICS OF THE DOSE-DEPENDENT UPTAKE OF PROPYLTHIOURACIL BY THYROID-GLAND INVIVO - EFFECTS OF THYROTROPIN, IODIDE OR PHENOBARBITAL PRETREATMENT

Dose dependency of propylthiouracil (PTU) uptake by the thyroid gland was studied in intact adult male rats after a single i.p. dose of PTU. PTU pharmacokinetics in rat serum, liver and lung were independent of the size of this single dose of PTU. 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. At serum PTU concentrations of 5 .mu.g/ml or above, thyroid to serum (T/S) PTU ratios are independent of PTU dose and serum concentration. Changes in the functional status of the thyroid changed the relationship between serum and thyroidal PTU concentrations. Thyroxine administration prior to an i.p. PTU dose of 5 mg/kg reduced ratios of T/S PTU concentrations. 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 KI or phenobarbital prior to PTU increased T/S PTU ratios, suggesting an effect of TSH on PTU metabolism in the thyroid.