Metabolism and Pharmacokinetics of Novel Selective Vascular Endothelial Growth Factor Receptor-2 Inhibitor Apatinib in Humans s

Apatinib is a new oral antiangiogenic molecule that inhibits vascular endothelial growth factor receptor-2. The present study aimed to determine the metabolism, pharmacokinetics, and excretion of apatinib in humans and to identify the enzymes responsible for its metabolism. The primary routes of apatinib biotransformation inclu-ded E- and Z-cyclopentyl-3-hydroxylation, N-dealkylation, pyridyl-25-N-oxidation, 16-hydroxylation, dioxygenation, and O-glucuronidation after 3-hydroxylation. Nine major metabolites were confirmed by comparison with reference standards. The total recovery of the administered dose was 76.8 % within 96 hours postdose, with 69.8 and 7.02 % of the administered dose excreted in feces and urine, respectively. About 59.0 % of the administered dose was excreted unchanged via feces. Unchanged apatinib was detected in negligible quantities in urine, indicating that systemically avail