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After administration of 0.01% levothyroxine sodium (T4-Na) powder (TZ-T4 : p.o.) and a solution of T4-Na (p.o. and i.v.) to hypothyroid dogs (Tx-D) and euthyroid dogs (Eu-D), the plasma levels of L-thyroxine (T4), liothyronine (T3) and thyroid-stimulating hormone (TSH) were determined by radioimmunoassay. The amount of L-thyroxine bound to plasma protein and the urinary excretion of T4 were studied in Tx-D. 1. TSH level was increased in Tx-D 3 to 7 times higher than in Eu-D for 7-12 days after thyroidectomy. 2. T4 level in Tx-D after a single oral administration of TZ-T4 (100 mg/kg) was similar to that of Eu-D treated with water. 3. A single oral administration of TZ-T4 gave the dose-dependent plasma half-life of T4. These results suggested the excretion of excess T4 as a physiological function. 4. A single oral administration of TZ-T4 (100 mg/kg, corresponding to 10 μg/kg as T4-Na) gave about the same bioavailability as that of T4-Na solution (10 μg/kg). 5. T4 level reached the plateau after consecutive administration of TZ-T4 (100 mg/kg/day, 7 days). T3 level was unchanged for 21 days. TSH level was attenuated to one-half (8.3 ng/ml) of the initial value, though still higher than Eu-D (1.5 ng/ml). 6. The amount of T4 bound to plasma protein was slightly increased by thyroidectomy.

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Studies on the Metabolic Fate of Levothyroxine-Sodium. (2): Plasma Concentration of T4, T3 and TSH, Urinary Excretion and Protein Binding in Thyroidectomized Dogs.