K. He, B. He, James E Grace
Nov 16, 2006
Citations
3
Influential Citations
47
Citations
Journal
Blood
Abstract
Apixaban is a potent, orally available, highly selective, and reversible factor Xa inhibitor, and currently under development for prevention and treatment of thrombosis. The preclinical pharmacokinetic and metabolism attributes of apixaban feature a small volume of distribution, a low systemic clearance, good oral bioavailability, multiple elimination pathways and minimal potential for drug-drug interactions. Apixaban is well absorbed in chimpanzees, dogs and rats with a mean oral bioavailability of 51, 88 and 34%, respectively. The mean volume of distribution of apixaban is 0.17, 0.29 and 0.31 L/kg in chimpanzees, dogs and rats, respectively, suggesting apixaban is primarily distributed (30–50%) to blood where the therapeutic action resides. The small volume is not due to extensive plasma protein binding, but possibly attributed to limited extravascular tissue distribution, given that the unbound fraction is approximately 13, 5, 8 and 4% in human, chimpanzee, dog and rat serum, respectively. The systemic clearance is