title: Factors influencing trough and 90-minute plasma dabigatran etexilate concentrations among patients with non-valvular atrial fibrillation.
abstract: BACKGROUND
  Dabigatran etexilate, a direct oral anti-coagulation agent, is used in the prevention of thromboembolism in patients with non-valvular atrial fibrillation (NVAF). However, for reasons that are not fully understood, plasma dabigatran etexilate concentrations (PDC) vary significantly among patients.
  
  
  METHODS
  We measured trough and 90min PDC in 98 patients with NVAF. To elucidate the cause of variations in PDC, we determined correlations between PDC and various factors including renal function, co-administration of a P-glycoprotein inhibitor, and the effects of three single nucleotide polymorphisms (SNPs) of the P-glycoprotein intestinal efflux transporter. To further determine the cause of PDC variations, we examined the relationship between PDC, activated partial prothrombin time (APTT), and D-dimer (DD) levels, which are surrogate markers for thrombotic risk.
  
  
  RESULTS
  Multivariate analysis showed significant relations among creatinine, creatinine clearance, and CHA2D2-VaSc scores (p=0.04, p=0.01, and p=0.04, respectively). In addition, creatinine and creatinine clearance were significantly correlated with trough and 90min PDC (p<0.01), respectively. There was a clear linear relation between PDC and APTT, but not DD levels. However, higher DD levels (>0.5μg/mL) were associated with lower trough and 90min PDCs.
  
  
  CONCLUSIONS
  Renal function and CHA2D2-VaSc scores affect PDC, suggesting these may be primary factors influencing the wide variation observed in PDCs under these conditions. Variations in APTT can primarily be explained by variations in PDC; patients with lower PDCs may have a higher risk of thromboembolism events.
authors.affiliation: Division of Cardiology, Shimada Hospital Ogori , Japan. Electronic address: hidetomi@zc5.so-net.ne.jp.
authors.forename: Hideharu
authors.initials: H
authors.lastname: Tomita
authors.affiliation: Department of Clinical Pharmacology, Gunma University Maebashi, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Araki
authors.affiliation: Division of Cardiology, Saiseikai Futsukaichi Hospital Chikushino, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kadokami
authors.affiliation: Department of Hospital Pharmacy, Faculty of Medicine, University of the Ryukyus Okinawa, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Division of Cardiology, Saiseikai Futsukaichi Hospital Chikushino, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Nakamura
authors.affiliation: Division of Cardiology, Aso Izuka Hospital Izuka, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Imamura
authors.affiliation: Division of Cardiology, Saiseikai Futsukaichi Hospital Chikushino, Japan.
authors.forename: Takaya
authors.initials: T
authors.lastname: Fukuyama
authors.affiliation: Department of Clinical Pharmacology, Gunma University Maebashi, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nagano
authors.affiliation: Division of Cardiology, Shimada Hospital Ogori , Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Hashimoto
authors.affiliation: Division of Cardiology, Shimada Hospital Ogori , Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Uematsu
authors.affiliation: Division of Cardiology, Saiseikai Futsukaichi Hospital Chikushino, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Hosokawa
authors.affiliation: Department of Clinical Pharmacology, Gunma University Maebashi, Japan.
authors.forename: Koujirou
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Department of Clinical Pharmacology & Therapeutics, University of the Ryukyus Okinawa, Japan.
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Ueda
authors.affiliation: Sleep Apnea Center, Kyushu University Hospital Fukuoka, Japan.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Ando
mesh_terms: D000991:Antithrombins / Q000008:administration & dosage / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000097:blood / Q000188:drug therapy*; D000069604:Dabigatran / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D012307:Risk Factors
chemical_list: D000991:Antithrombins; D000069604:Dabigatran
keywords: Activated partial prothrombin time; D-dimer; Dabigatran; Plasma dabigatran concentration