TY - JOUR T1 - Pharmacokinetics, Biotransformation, and Mass Balance of Edoxaban, a Selective, Direct Factor Xa Inhibitor, in Humans JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 2250 LP - 2255 DO - 10.1124/dmd.112.046888 VL - 40 IS - 12 AU - Mohinder S. Bathala AU - Hiroshi Masumoto AU - Toshihiro Oguma AU - Ling He AU - Chris Lowrie AU - Jeanne Mendell Y1 - 2012/12/01 UR - http://dmd.aspetjournals.org/content/40/12/2250.abstract N2 - This study determined the mass balance and pharmacokinetics of edoxaban in humans after oral administration of [14C]edoxaban. After oral administration of 60 mg (as active moiety) of [14C]edoxaban to six healthy male subjects, serial blood/plasma and urinary and fecal samples were collected for up to 168 h postdose. All samples were analyzed for total radioactivity by liquid scintillation counting and for concentrations of edoxaban and four metabolites in plasma, urine, and fecal samples by either high-performance liquid chromatography/tandem mass spectrometry method using multiple reaction modes, or a liquid chromatography radiometric method. The mean recovery of radioactivity was >97% of the administered radioactive dose, with 62.2% eliminated in feces and 35.4% in urine. Unchanged edoxaban accounted for the majority of radioactivity, with 49.1 and 23.8% of the dose as parent observed in feces and urine, respectively. Unchanged edoxaban was the most abundant species in plasma, with a mean area under the curve (AUC)0−∞ of 1596 ng · h/ml. The next most abundant species was metabolite M4, with a mean AUC0−∞ 147 ng · h/ml. The mass balance of edoxaban was well described, with unchanged edoxaban as the most abundant component of total radioactivity. Edoxaban is eliminated through multiple pathways, but each accounts for only a small amount of overall elimination. ER -