We have investigate the absorption, excretion and metabolism of 3H-TJN-101 following single oral administration of the drug (4 mg/kg) in male dogs.
1. The concentration of radioactivity in the blood was determined by the dry method. The Cmax of 1666ng/ml (TJN-101 base) was reached at 45 min after administration. Then, the radioactivity decreased with a half life of 3.6hr from 1 to 8hr, with a half life of 9.7hr from 12 to 48hr, and with a half life of 2.4 days from 72 to 168hr. The AUC for the first 168hr after treatment was 11.1μg·hr/ml. Plasma levels of radioactivity, as determined by the dry method, reached a maximun (2813ng/ml) at 45 min after treatment and subsequently followed a course smilar to that of its blood level. The ratio of unstable tritium in the plasma was 8 % or less until 12hr, 22% at 24hr, 58% at 48hr, 77% at 72hr, and 85 ?? 87% on and after 96hr. The distribution ratio of radioactivity in blood cell, determined simultaneously, was 4.1 ?? 13.1% until 72hr and 20.5 ?? 40.7% on and after 96hr.
2. Within 168hr after oral administration, radioactivity in the urine and feces in male dogs was 40.1% and 54.8% of the dose, respectively. Unstable tritium was not detected in any urine samples collected during the 168hr after dosing.
3. The ratio of plasma protein binding of radioac tive substances in vivo was 77.0% at 15 min after treatment and subsequently decreased with time, reaching 55.8% at 8hr.
4. When the plasma specimens collected at 15, 45, and 120 min were exam ined for unchanged TJN-101, the ratio of unchanged TJN-101 to total radioactivity was 65.2% at 15 min and decreased with time, thereafter, reaching 55.2% at 2hr. The ratio of Met. A-III was 7.1 % at 15 min and increased with time, thereafter, accounting for 13.3% at 2hr. For all samples collected on the different occasions, the percentage of radioactivity which remained at origin was 25% or more. After enzymatic hydrolysis, this percentage decreased to below 5.5%, while the percentage of the parent compound increased to 64.5 ?? 74.2%. In the case of urine and feces collected during first 48hr after dosing, radioactivity was mainly present as Met. A-III, Met. B and Met. F.
