Abstract
The absorption, distribution, and excretion of KAA-276 were studied in male rats after intratracheal administration of 3H-KAA-276.
1. The radioactivity level in plasma reached a maximum at 5 min after intratracheal administration of 3H-KAA-276 to male rats at a dose of 30μg/kg. The AUC at this dose was 17.8 ng eq. of KAA-276·hr/ml, which accounted for about 100% of the AUC observed after intravenous administration at the same dose. The Cmax and the AUC were increased in a dose-dependent manner at the dose range of 10 to 100 μg/kg.
2. The radioactivity levels in the lungs, trachea, liver, pituitary, kidneys, urinary bladder, and mandibular gland were high after administration of 3H-KAA-276 to the rats. Low levels were detected in the central nervous system, eyeballs, and testes.
3. The excretion of radioactivity in the urine and feces was 17.8% and 82.1% of the dose, respectively, by 168 hr after administration. The excretion of radioactivity in the bile was 75.3% of the dose within 48 hr. Moreover, almost 40% of the biliary excreta was re-absorbed and excreted in the bile and urine.
