title: Evaluation of the chromogenic anti-factor IIa assay to assess dabigatran exposure in geriatric patients with atrial fibrillation in an outpatient setting.
abstract: BACKGROUND
  Dabigatran etexilate may be underutilized in geriatric patients because of inadequate clinical experience in individuals with severe renal impairment and post-marketing reports of bleeding events. Assessing the degree of anticoagulation may improve the risk:benefit ratio for dabigatran. The aim of this prospective study was to identify whether therapeutic drug monitoring of dabigatran anticoagulant activity using a chromogenic anti-factor IIa assay is a viable option for therapy individualization.
  
  
  METHODS
  Plasma dabigatran concentration was assessed in nine patients with nonvalvular atrial fibrillation aged 75 years or older currently receiving dabigatran etexilate for prevention of stroke, using an anti-factor IIa chromogenic assay and HPLC-MS/MS. Trough concentrations were evaluated on two separate occasions to determine intrapatient variation.
  
  
  RESULTS
  Blood was collected at 13.1 ± 2.3 h (mean ± SD) post dose from patients prescribed dabigatran etexilate 150 mg twice daily (5/9 patients) or dabigatran etexilate 75 mg twice daily (4/9 patients). Results from the anti-factor IIa chromogenic assay correlated with dabigatran concentrations as assessed by HPLC-MS/MS (r (2)  = 0.81, n = 16). There was no correlation between dabigatran trough values taken at separate visits (r (2)  = 0.002, n = 7). Furthermore, there was no correlation found between the drug concentrations and patients' renal function determined by both creatinine and cystatin-C based equations. None of the patients enrolled in the study were in the proposed on-therapy trough range during at least one visit.
  
  
  CONCLUSIONS
  The chromogenic anti-factor IIa assay demonstrated similar performance in quantifying dabigatran plasma trough concentrations to HPLC-MS/MS. Single measurement of dabigatran concentration by either of two methods during routine visits may not be reliable in identifying patients at consistently low or high dabigatran concentrations.
authors.affiliation: Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, USA.
authors.forename: Luigi
authors.initials: L
authors.lastname: Brunetti
authors.affiliation: Department of Medicine, Robert Wood Johnson University Hospital-Somerset, Somerville, USA.
authors.forename: Betty
authors.initials: B
authors.lastname: Sanchez-Catanese
authors.affiliation: Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, USA.
authors.forename: Leonid
authors.initials: L
authors.lastname: Kagan
authors.affiliation: Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, USA.
authors.forename: Xia
authors.initials: X
authors.lastname: Wen
authors.affiliation: Chemical Analytical Core Laboratory, Environmental and Occupational Health Sciences Institute, Rutgers, The State University of New Jersey, Piscataway, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: Chemical Analytical Core Laboratory, Environmental and Occupational Health Sciences Institute, Rutgers, The State University of New Jersey, Piscataway, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Buckley
authors.affiliation: Pathology and Diagnostic Inv., Michigan State University, East Lansing, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: Luyendyk
authors.affiliation: Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, USA.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Aleksunes
keywords: Atrial fibrillation; Chromogenic anti-factor IIa; Dabigatran; Geriatric; HPLC-MS/MS