Pharmacokinetics of 3,5,3'-triiodothyroacetic acid and its effects on serum TSH levels.

Abstract

3,5,3'-triiodothyroacetic acid is an effective inhibitor of TSH secretion in central hyperthyroidism. Serum, 3,5,3'-triiodothyroacetic acid was measured with an RIA preceded by immunoprecipitation. An anti-3,5,3'-triiodothyroacetic acid antibody was obtained in rabbits, using 3,5,3'-triiodothyroacetic acid coupled to hemocyanin and diazotized benzidine as antigen (cross-reactivity with T4, T3, tetraiodothyroacetic acid was 0.2, 1.1, and 5%, respectively). Endogenous 3,5,3'-triiodothyroacetic acid levels could not be detected in 14 euthyroid, 10 hypothyroid and 10 hyperthyroid sera (detection limit 0.055 nmol/l). Kinetic studies were performed in 6 healthy male subjects who received an oral and an iv dose of 1050 micrograms of 3,5,3'-triiodothyroacetic acid. The serum measurements were analysed according to a non-compartmental method. The half-life of 3,5,3'-triiodothyroacetic acid was 6 h 22 min +/- 29 min, the volume of distribution was 114 +/- 9 1/70 kg, and the plasma clearance rate was 298 +/- 141.(70 kg)-1.day-1. Highest 3,5,3'-triiodothyroacetic acid levels were measured after 40 min (for T3 2-3 h) and its absorption was 67 +/- 6%. The nadir of the mean TSH levels was 0.72 +/- 0.09 mU/l 6 h after 3,5,3'-triiodothyroacetic acid administration. However, the time course of serum TSH response did not differ from that obtained after administration of 37.5 micrograms T3. The dose-response effect for TSH was studied using oral doses of 350, 700, 1400 and 2800 micrograms 3,5,3'-triiodothyroacetic acid. TSH was measured 9 h after 3,5,3'-triiodothyroacetic acid administration at 17.00 h, and compared with control serum TSH levels obtained at 08.00 h (1.53 +/- 0.11) and at 17.00 h the day before the test (1.87 +/- 0.11). They were 1.05 +/- 0.15 (N = 9, mean +/- SEM), 0.83 +/- 0.08 (N = 24), 0.66 +/- 0.06 (N = 24), and 0.43 +/- 0.02 mU/l (N = 6), respectively. In conclusion, TSH inhibition by 3,5,3'-triiodothyroacetic acid is similar to T3, with a potency ratio of 1 to 18.