Disposition of Posatirelin (1): Plasma Level, Tissue Level, Brain Distribution and Excretion after Single Intravenous Administration in Rats

The plasma level, tissue level, brain distribution and excretion of the radioactivity were investigated in rats after intravenous administration of [14C]posatirelin at a dose of 20 mg/kg. 1. The plasma level of radioactivity at 5 min after intravenous administration was about 71 μg eq·/mll, and decreased biphasically thereafter with half lives of about 18 min (α-phase) and 15 hr (β-phase). The AUC (0-∞) was about 47 μg eq·hr/ml. 2. At 5 min after administration, the kidney showed the highest level of radioactivity, followed by the plasma, aorta, urinary bladder, skin, pancreas, liver and lung. The brain level of radioactivity was the lowest among the tissue levels examined. Most tissue levels decreased essentially in parallel with plasma level. 3. At 5 min after administration, the mesolimbic area and cerebellum levels of radioactivity we re significantly higher than those in other parts of the brain. The cerebral cortex, cerebellar cortex, fornix, triangularis septal nucleus, hippocampal commissure, colliculus superior and ventricle wall were found to exerthigh levels of the radioactivity. 4. The cumulat ive excretion of radioactivity in urine, feces and expired air were 70.9%, 12.3% and 15.1%, respectively, within 72 hr after administration. Within 48 hr after administration, 7.2% of dosed radioactivity was excreted in the bile. 5. [14C]Posatirelin was hardly bound to rat plasma and human serum proteins.