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 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.
Footnotes
Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
ABBREVIATIONS:
- FXa
- factor Xa
- PK
- pharmacokinetics
- HPLC
- high-performance liquid chromatography
- MRM
- multiple reaction monitoring
- LC-MS/MS
- high-performance liquid chromatography/tandem mass spectrometry
- AE
- adverse event
- AUC
- area under the curve
- P450
- cytochrome P450.
- Received May 22, 2012.
- Accepted August 30, 2012.
- Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics
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