title: Pharmacokinetics, biotransformation, and mass balance of edoxaban, a selective, direct factor Xa inhibitor, in humans.
abstract: 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 AUC(0-∞) 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.
authors.affiliation: Daiichi Sankyo Pharma Development, Edison, New Jersey, USA.
authors.forename: Mohinder S
authors.initials: MS
authors.lastname: Bathala
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Masumoto
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Oguma
authors.forename: Ling
authors.initials: L
authors.lastname: He
authors.forename: Chris
authors.initials: C
authors.lastname: Lowrie
authors.forename: Jeanne
authors.initials: J
authors.lastname: Mendell
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001711:Biotransformation; D002250:Carbon Radioisotopes; D015951:Factor Xa / Q000378:metabolism; D065427:Factor Xa Inhibitors; D005243:Feces / Q000737:chemistry; D006801:Humans; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D013844:Thiazoles / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
chemical_list: D002250:Carbon Radioisotopes; D065427:Factor Xa Inhibitors; D011725:Pyridines; D013844:Thiazoles; D015951:Factor Xa; C552171:edoxaban