Propylthiouracil (PTU) Pharmacology in the Rat,I. Serum and Thyroid PTU Measurements by Radioimmunoassay*

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Abstract
A highly sensitive and specific RIA [radioimmunoassay] for propylthiouracil (PTU) which uses 125I-labeled PTU as the radioactive ligand was developed. 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 wk) and long-term (1 mo.) PTU treatment at doses of 0.0001-0.05%. Serum PTU was a linear function of the PTU dose (r = 0.99; P < 0.001), while thyroid PTU was a linear function of the logarithm of the PTU dose (r = 0.99; P < 0.001). Serum PTU levels were higher after 1 mo. of treatment than after administration for 1 wk, probably because steady state conditions were not achieved after 1 wk. At several doses thyroid PTU levels were also higher after 1 mo. 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.