Abstract
We have developed a highly sensitive and specific RIA for propylthiouracil (PTU) which uses 125I-labeled PTU as the radioactive ligand. At a final antibody dilution of 1:10,000, the detection limit for PTU was 100 pg; cross-reactivity with circulating, urinary, and intrathyroid PTU metabolites was negligible. Using this assay, serum and thyroid PTU levels were determined after short term (1 week) and long term (1 month) PTU treatment at doses of 0.0001-0.05%. Serum PTU was a linear function of the PTU dose (r = 0.99; P less than 0.001), whereas thyroid PTU was a linear function of the logarithm of the PTU dose (r = 0.99; P less than 0.001). Serum PTU levels were higher after 1 month of treatment than after administration for 1 week, probably because steady state conditions were not achieved after 1 week. At several doses, thyroid PTU levels were also higher after 1 month of treatment, but the differences were not as striking as those seen in the serum levels. The pharmacokinetic data are consistent with a multicompartmental model for PTU distribution. The logarithmic relationship between thyroid PTU and PTU dose suggests a saturable uptake mechanism for PTU by the thyroid; inhibition of thyroid PTU uptake by PTU itself could also explain these observations.
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