Determination of edoxaban equivalent concentrations in human plasma by an automated anti-factor Xa chromogenic assay

• Published in: Thrombosis research 2017-07, Vol.155, p.121-127
• Main Authors: He, Ling, Kochan, Jarema, Lin, Min, Vandell, Alexander, Brown, Karen, Depasse, Francois
• Format: Article
• Language: English
• Subjects: Adult; Anti-FXa assay; Blood Coagulation - drug effects; Blood Coagulation Tests - methods; Blood Specimen Collection - methods; Chromatography, Liquid - methods; Coagulation assay; Direct oral anticoagulants; Drug Monitoring - methods; Edoxaban; Factor Xa - metabolism; Factor Xa Inhibitors - administration & dosage; Factor Xa Inhibitors - adverse effects; Factor Xa Inhibitors - blood; Female; Hematology, Oncology and Palliative Medicine; Humans; Laboratory monitoring; Male; Middle Aged; Pharmacokinetics; Pyridines - administration & dosage; Pyridines - adverse effects; Pyridines - blood; Tandem Mass Spectrometry - methods; Thiazoles - administration & dosage; Thiazoles - adverse effects; Thiazoles - blood
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2017.05.005

Abstract Introduction This phase I, open-label, multiple-dose, two-treatment study assessed the relationship between edoxaban equivalent concentration derived from an anti-FXa assay with the summed concentration of edoxaban and its active metabolite, M-4, as assessed by liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS). This study also assessed the relationship between edoxaban plasma concentrations assessed by LC/MS/MS in sodium citrate and lithium heparin tubes. Materials and methods Healthy volunteers were randomized to receive once-daily edoxaban 60 mg or 90 mg for 5 days (15 participants per treatment group). Serial blood samples were collected for analysis by LC/MS/MS and by the anti-FXa assay. Edoxaban equivalent levels were assessed using a commercially available anti-FXa activity assay with an edoxaban-specific setup. Results and conclusions The day 5 concentration estimates were significantly correlated between the 2 assays ( P < 0.0001 for both edoxaban doses). The geometric least squares mean (GLSM) ratio (90% confidence interval) for edoxaban equivalent concentrations vs edoxaban + M-4 concentrations was 114.3% (108.2–120.8) for edoxaban 60 mg ( P < 0.0001) and 113.0% (107.1–119.2) for edoxaban 90 mg ( P = 0.0002). The GLSM ratio for edoxaban concentrations in sodium citrate vs lithium heparin tubes for 60-mg and 90-mg edoxaban doses were 82.8% (78.5–87.3) and 83.9% (79.1–89.0), respectively. In this study, an anti-FXa chromogenic assay with edoxaban-specific calibrators and controls demonstrated good accuracy in estimating edoxaban concentrations across a wide range of concentrations relative to LC/MS/MS at steady state following the administration of once-daily edoxaban for 5 days.