Human Radiolabeled Mass Balance Study

Purpose: Compound A is a novel, potent, and highly selective tyrosine kinase inhibitor. This study was conducted to investigate the metabolism, excretion, and pharmacokinetics after a single oral dose to healthy men.

Methods: Six subjects were administrated an oral suspension containing 5 mg of ¹⁴C-labeled Compound A (100 μCi) in a fasted state. Blood and excreta samples were collected at the designated time points or intervals for pharmacokinetics and radiometric analyses. Safety assessments were conducted throughout the study.

Results: Over a 336-h post-dose collection period, compound A was well tolerated and absorbed rapidly, mean recovery was 90.11% of the radiolabeled dose, with 60.31% in urine and 29.80% in feces. Parent compound was the predominant circulating component, were cleared from circulation with terminal half-lives more than 30h. M379-3 was the major circulating metabolite, accounting for 17.31% of the total radioactivity. An additional seven circulating metabolites were identified, each accounting for less than 5% of the total radioactivity. In urine, compound A accounted for only 0.50% of the administered dose. three major metabolites M285, M381, and M409-4 were identified accounting for 10.48, 21.16, and 8.92% of the dose, respectively. In feces, compound A accounted for 5.34% of the dose. M205, M365-2, and M380 were the major metabolites, accounting for 2.29, 3.30, and 2.59% of the dose, respectively. Compound A was extensively metabolized prior to excretion, and urine was the major route of excretion.