YM466 is a novel factor Xa inhibitor for the treatment of thrombosis. The absorption, distribution, metabolism and excretion of YM466 were investigated in male Fisher rats after a single oral administration. YM466 was absorbed rapidly from all segments of the gastrointestinal tract except the stomach. After oral dosing, the plasma concentration of 14C‐YM466 reached a maximum within 0.5h, and declined rapidly with an elimination half‐life of 0.64h. The unchanged YM466 accounted for almost all of its radioactivity, suggesting a minimal metabolism in rats. This was also supported by the finding that no metabolites were observed in bile and urine after oral dosing of 14C‐YM466. The distribution of 14C‐YM466 in tissue was evaluated and the liver and kidney were the organs with radioactivity concentrations consistently higher than that of plasma. Cumulative biliary and urinary excretion of radioactivity in bile duct‐cannulated rats was 29.5% and 7.6%, respectively, indicating prominent excretion into bile after oral dosing. This was consistent with the finding that 76.1% and 25.2% of radioactivity dosed were excreted to faeces and urine, respectively, after i.v. dosing. These results suggest that YM466 was rapidly absorbed and then subjected to biliary excretion with a minimal metabolism after oral dosing to rats. Copyright © 2004 John Wiley & Sons, Ltd.