Studies on the Metabolic Fate of 3H-TJN-101. (I): Absorption, Distribution and Excretion following Single Oral Administration to Rats.

We investigated the absorption, distribution and excretion of 3H-TJN-101 following single oral administration of the drug in rats.1. The concentration of radioactivity in blood increased rapidly after oral administration of 4 mg/kg of 3H-TJN-101 in male rats and reached Cmax of 816ng/ml (TJN-101 base) at 0.75hr. Thereafter, the radioactivity decreased, with a half-life of 1. 1hr up to 4 hr and with a half-life of 7.6hr from 6 to 24hr after dosing. The concentration dropped below the detection limit at 48hr. The area under the concentration-time curve (AUC0-24h) was 3.12μg•hr/ml. Following oral administration of 0.8mg/kg of 3H-TJN-101 in male rats, both Cmax and AUC0-24hr were 12% of the values of the 4 mg/kg group. Cmax and AUC0-24h, following oral administration of 20mg/kg of 3H-TJN-101 were 5.4 and 9.2 times of the values of the 4 mg/ kg group, respectively.2. In female rats, at 0.75hr after oral administration of 4mg/kg of 3H-TJN-101, Cmax was 682ng/ml, and it decreased, with a half-life of 2.9hr up to 8hr after dosing. Cmax and AUC0-24h, were 84% and 1.3 times of those in the male rats, respectively.3. Tissue radioactivity after oral administration of 4mg/kg of 3H-TJN-101 reached the maximum level within 0.25 to 0.75hr, being higher in the liver, and lower in the central nervous system, testis, and eyeball.4. Within 168hr after oral administration of 4mg/kg of 3H-TJN-101, radioactivity in the urine and feces in male rats was 13.6% and 83.1% of administered dose, respectively, and that in female rats was 20.9% and 73.9% of the dose, respectively.5. Within 48hr after dosing, 91.1% of the total radioactivity was detected in the bile and 4.5% in the urine, as determined simultaneously.6. Within 48hr after intraduodenal administration of radioactivie bile obtained from other rats which had been administered 3H-TJN-101 orally, 52.0% of injected radioactivity was excreted in the bile and 4.0% in the urine.