Studies on the Metabolic Fate of Levothyroxine-Sodium. (1): Plasma Concentration of T4, T3 and TSH, Protein Binding and the Hepatic Drug-Metabolizing Enzyme Activity in Thyroidectomized Rats.

Abstract

Plasma levels of L-thyroxine (T4), liothyronine (T3) and thyroid-stimulating hormone (TSH), plasma protein binding of T4 and drug-metabolizing activities of liver microsomes were studied in thyroidectomized rat (Tx-R) treated with T4-Na (30 μg/kg, p. o.). 1. The plasma leve ls of T4 in Tx-R treated with T4-Na were similar to those in euthyroid rat (Eu-R) treated with vehicle. 2. The Cmax of T4 occurred 8 hr after a single oral administration and plasma levels decayed with the T1/2 of 58.2 hr. The bioavailability of T4 was 34.7 %. 3. The elevated TSH due to th yroidectomy decreased to the level of Eu-R during consecutive administration of T4-Na. 4. The growth rates in Tx-R during consecutive administration of vehicle and T4-Na for 21 days were 0.2 and 2.8 g/day, respectively. 5. The amount of T4 bound to plasma protein increased by thyroidectomy and then decreased during consecutive administration of T4-Na. 6. Thyroidectomy did not affect the cyt. P-450 in liver microsomes, while the cyt. b5 increased and NADPH-cyt. c reductase, aminopyrine N-demethylase and arylhydrocarbon hydroxylase activities were decreased. Consecutive administration of T4-Na slightly improved those affections.