Rivaroxaban is a novel, oral, direct factor Xa inhibitor for the prevention and 
treatment of thromboembolic disorders. The objective of this study was to 
investigate the in vivo metabolism and excretion of rivaroxaban in rats, dogs, 
and humans. Single doses of [(14)C]rivaroxaban (3 and 1 mg/kg) were administered 
to rats (orally/intravenously) and dogs (orally), respectively. A single oral 
dose of [(14)C]rivaroxaban (10 mg) was administered to healthy human males (n = 
4). Plasma and excreta were collected and profiled for radioactivity. Recovery 
of total radioactivity was high and > or = 92% in all species. Unchanged 
rivaroxaban was the major compound in plasma at all time points investigated, 
across all species. No major or pharmacologically active circulating metabolites 
were detected. Rivaroxaban and its metabolites were rapidly excreted; urinary 
excretion of radioactivity was 25 and 52%, and fecal excretion was 67 and 43% of 
the dose in rats and dogs, respectively. In humans, 66% of the dose was excreted 
renally (36% unchanged drug) and 28% in the feces. Radioactivity profiles in 
excreta were similar across species. Three metabolic pathways were identified: 
oxidative degradation of the morpholinone moiety (major pathway) and hydrolysis 
of the central amide bond and of the lactam amide bond in the morpholinone ring 
(minor pathways). M-1, the main metabolite in excreta of all species, was 
eliminated via both renal and fecal/biliary routes. In total, 82 to 89% of the 
dose administered was assigned to unchanged rivaroxaban and its metabolites in 
the excreta of rats, dogs, and humans.