TY - DATA T1 - Absorption, distribution, metabolism, and excretion of mTOR kinase inhibitor CC-223 in rats, dogs, and humans PY - 2017/12/20 AU - Zeen Tong AU - Christian Atsriku AU - Usha Yerramilli AU - Xiaomin Wang AU - Jim Nissel AU - Yan Li AU - Sekhar Surapaneni UR - https://tandf.figshare.com/articles/journal_contribution/Absorption_distribution_metabolism_and_excretion_of_mTOR_kinase_inhibitor_CC-223_in_rats_dogs_and_humans/5722387 DO - 10.6084/m9.figshare.5722387.v1 L4 - https://ndownloader.figshare.com/files/10057063 KW - Accelerator mass spectrometry KW - ADME KW - mTOR kinase inhibitor KW - species comparison N2 - 1. The absorption, distribution, metabolism, and excretion of CC-223 were studied following a single oral dose of [14C]CC-223 to rats (3 mg/kg; 90 μCi/kg), dogs (1.5 mg/kg; 10 μCi/kg), and healthy volunteers (20 mg; 200 nCi). 2. CC-223-derived radioactivity was widely distributed in rats. Excretion of radioactivity was rapid and nearly complete from rats (87%), dogs (78%), and humans (97%). Feces was the major excretion pathway for rats (67%) and dogs (70%), whereas urine (57.6%) was the major elimination route for humans. Urine and bile each contained approximately 20% administered radioactivity in rats, whereas bile (20%) played a more important role than urine (<10%) in the excretion of absorbed radioactivity in dogs. Based on excretion data, CC-223 had good absorption, with greater than 56%, 29%, and 57% of the oral dose absorbed in rats, dogs, and humans, respectively. 3. CC-223 was the prominent radioactive component in circulation of rats (>71% of the exposure to total radioactivity) and dogs (≥45.5%), whereas M1 (76.5%) was the predominant circulating metabolite in humans. M1 and M1-derived metabolites accounted for >66% of human dose. CC-223 was extensively metabolized in rats, dogs, and humans through glucuronidation, O-demethylation, oxidation, and combinations of these pathways. ER -