Pharmacokinetics, Biotransformation, and Mass Balance of Edoxaban, a Selective, Direct Factor Xa Inhibitor, in Humans
- 30 August 2012
- journal article
- Published by American Society for Pharmacology & Experimental Therapeutics (ASPET) in Drug Metabolism and Disposition
- Vol. 40 (12), 2250-2255
- https://doi.org/10.1124/dmd.112.046888
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.Keywords
This publication has 13 references indexed in Scilit:
- Effects of Food on the Pharmacokinetics of Edoxaban, an Oral Direct Factor Xa Inhibitor, in Healthy VolunteersThe Journal of Clinical Pharmacology, 2011
- 2011 ACCF/AHA/HRS Focused Updates Incorporated Into the ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial FibrillationCirculation, 2011
- Factor Xa and thrombin as targets for new oral anticoagulantsThrombosis Research, 2011
- Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort studyBMJ, 2011
- Evaluation of the novel factor Xa inhibitor edoxaban compared with warfarin in patients with atrial fibrillation: Design and rationale for the Effective aNticoaGulation with factor xA next GEneration in Atrial Fibrillation–Thrombolysis In Myocardial Infarction study 48 (ENGAGE AF–TIMI 48)American Heart Journal, 2010
- A dose‐ranging study evaluating the oral factor Xa inhibitor edoxaban for the prevention of venous thromboembolism in patients undergoing total knee arthroplastyJournal of Thrombosis and Haemostasis, 2010
- Oral direct factor Xa inhibition with edoxaban for thromboprophylaxis after elective total hip replacementThrombosis and Haemostasis, 2010
- Randomised, parallel-group, multicentre, multinational phase 2 study comparing edoxaban, an oral factor Xa inhibitor, with warfarin for stroke prevention in patients with atrial fibrillationThrombosis and Haemostasis, 2010
- DU‐176b, a potent and orally active factor Xa inhibitor: in vitro and in vivo pharmacological profilesJournal of Thrombosis and Haemostasis, 2008
- Venous thromboembolism (VTE) in EuropeThrombosis and Haemostasis, 2007