Abstract
Quantitative blood levels of thyrotropin-releasinghormone (TRH) were determined a sensitive and specific radioimmunoassay after oral administration or intravenous injection of thyrotropin-releasing hormone tartrate monohydrate (TRH-T) in the rat, dog and human. A pharmacokinetic analysis after intravenous injection of the drug revealed biphasic elimination of the whole blood concentration following a two-compartment open model with a half-life in α-phase of 2.6 min and β-phase of 4.6 min in the rat (dose : 500 μg/kg); a half-life in α-phase of 3.2 min and β-phase of 18.1 min in the beagle-dog (dose : 146 μg/dog); a half-life in α-phase of 4.0 min and β-phase of 20.4 min in the human (dose : 730 μg/human). The absolute bioavailability of TRH after oral administration of TRH-T solution in 24h fasting rats were 1.5, 0.4 and 0.2% at 29.2, 146, and 730 mg/kg dosing levels, respectively (e.q. 20, 100, 500 mg/kg of TRH) compared with i.v. injection (dose : 500 μg/kg). In beagledogs, they were 12.6, 9.8, 5.6, and 2.92, 14.6, 29.2, and 146 mg/dog dosing levels, respectively (e.q. 2, 10, 20, and 100 mg/dog of TRH) compared with i.v. injection (dose : 146 μg/dog). Those of after meal in beagle-dogs were 6.0 and 2.3% at 2.92 and 29.2 mg/dog dosing levels (e.q. 2, and 20 mg/dog of TRH). Thus, TRH absorption showed apparent saturation and was decreased by food ingestion. The absolute bioavailability in the humans, who were administered 11.7 mg TRH-T (2.92 mg/tablet×four, e.q. 8 mg of TRH) two hours after meal, was 2.0% on the average, and thyroid stimulating hormone levels were significantly increased by oral administration of TRH-T tablets.
