Studies on the Metabolic Fate of 3H-TJN-101. (VI). Blood and Plasma Concentration Profiles and Excretion after Intravenous Administration to Rats and Dogs.

Abstract

The distribution (blood or plasma concentration) and excretion of 3H-TJN-101 were examined in male rats and dogs after intravenous administration (4 mg/kg). 1. In male rats, the blood level of radioactivity ranged from 1.00 to 1.13μg/ml (TJN-101 base) at 5 min through 1hr after dosing. Thereafter, the blood level decreased with a half-life of 1.4hr from 2 to 6hr, and with a half-life of 25hr from 8 to 72hr after drug treatment. The AUC for 168hr after treatment was 5.75μg·hr/ml. 2. Within 168hr after injection, the radioactivily excreted in urine and feces in male rats was 11.7% and 80.5% of the dose, respectively. In urine collected for 168hr, the unstable tritium equivalent to 1.2% of the administered radioactivity was detected. 3. When the concentration of radioactivity in the blood of male dogs was determined by the dry method, the level was 3.03μg/ml (TJN-101 base) at 5min, which was first measurment period after dosing. Thereafter, the blood level decreased with a half-life of 43min up to 45min, with a half-life of 2.6hr from 1 to 4hr, and with a half-life of 6.1hr from 6 to 24 hr after dosing. At 48hr, the blood level decreased below the detection limit. The AUC for 24hr after dosing was 8.56μg·hr/ml. The concentration of radioactivity in plasma, determined by the dry method, was 5.05μg/ml at 5min. Thereafter, plasma level followed a course similar to that of blood level. The ratio of unstable tritium in plasma was below 6 % until 12hr, 27% at 24hr, and 50 ?? 75% from 48 to 120hr. The distribution ratio of radioactivity in blood cell simultaneously determined was 4.7 ?? 14.0% during the first 24hr. 4. Within 168hr after injection, radioactivity excreted in urine and feces in male dogs was 38.9% and 60.0% of the dose, respectively.