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

RACHELLE HALPERN, DAVID S. COOPER, J. DAVID KIEFFER, VELIA SAXE, HEIDI MOVER, FARAHE MALOOF and E. CHESTER RIDGWAY

Thyroid Unit and Department of Medicine, Massachusetts General Hospital and Harvard Medical School Boston, Massachusetts 02114

Address requests for reprints to: Dr. David S. Cooper, Thyroid Unit,Massachusetts General Hospital, Boston, Massachusetts 02114.

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 < 0.001), whereas 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 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. (Endocrinology 113: 915, 1983)

Footnotes

^* A preliminary account of parts of this research was presented as Abstract T-5 at the 57th Meeting of the American Thyroid Association,Minneapolis, MN 1981. This work was supported by USPHS Grants AM-16791 and AM-07028.

Recipient of a New Investigator Award from the NIH (1-R23-AM-28465-01).

Received January 4, 1983.

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