title: Pharmacokinetics and Pharmacodynamics of the Nonvitamin K Antagonist Oral Anticoagulant Edoxaban When Administered Alone or After Switching from Rivaroxaban or Dabigatran Etexilate in Healthy Subjects.
abstract: OBJECTIVE
  Edoxaban is an oral, once-daily direct factor Xa inhibitor. To support the possibility that patients may choose to switch treatment from another nonvitamin K antagonist oral anticoagulant to edoxaban, this clinical study was conducted to evaluate the pharmacokinetic and pharmacodynamic effects of edoxaban after switching from rivaroxaban or dabigatran etexilate to edoxaban.
  
  
  METHODS
  In this open-label, three-period, crossover study, healthy subjects received 3 days of edoxaban 60 mg daily, rivaroxaban 20 mg daily, or dabigatran etexilate 150 mg twice daily, followed by edoxaban 60 mg on day 4.
  
  
  RESULTS
  Day 4 edoxaban pharmacokinetic parameters were similar for all treatments. The peak effect of edoxaban on prothrombin time (PT) after 4 days of edoxaban only was 21.8 ± 2.46 s; after switching from rivaroxaban to edoxaban, peak effect on PT was similar at 21.8 ± 2.88 s. After switching from dabigatran etexilate to edoxaban, least squares mean activated partial thromboplastin time (aPTT) at 2 h after administration was 47.6 vs 35.0 s for edoxaban alone. The treatment difference was 12.8 s (95% confidence interval 10.5-15.1; p < 0.0001). Post hoc analysis revealed that predose aPTT was elevated on day 3 of dabigatran etexilate administration, and on day 4, indicating a carryover effect from dabigatran. All treatments were well tolerated and there were no safety concerns upon switching, with no increased risk of bleeding.
  
  
  CONCLUSIONS
  The study results suggest that switching to edoxaban from either rivaroxaban or dabigatran etexilate at the time of the next dose is well tolerated and maintains coagulation status.
authors.affiliation: Daiichi Sankyo Pharma Development, 399 Thornall St., Edison, NJ, 08837, USA.
authors.forename: Dolly A
authors.initials: DA
authors.lastname: Parasrampuria
authors.affiliation: Quintiles, Overland Park, KS, USA.
authors.forename: Doris
authors.initials: D
authors.lastname: Weilert
authors.affiliation: Daiichi Sankyo, Inc., Parsippany, NJ, USA.
authors.forename: Jen-Fue
authors.initials: JF
authors.lastname: Maa
authors.affiliation: Daiichi Sankyo Pharma Development, 399 Thornall St., Edison, NJ, 08837, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Dishy
authors.affiliation: Daiichi Sankyo Pharma Development, 399 Thornall St., Edison, NJ, 08837, USA.
authors.forename: Jarema
authors.initials: J
authors.lastname: Kochan
authors.affiliation: Daiichi Sankyo Pharma Development, 399 Thornall St., Edison, NJ, 08837, USA.
authors.forename: Minggao
authors.initials: M
authors.lastname: Shi
authors.affiliation: Daiichi Sankyo Pharma Development, 399 Thornall St., Edison, NJ, 08837, USA. kbrown@dsi.com.
authors.forename: Karen S
authors.initials: KS
authors.lastname: Brown
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000925:Anticoagulants / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D019540:Area Under Curve; D018592:Cross-Over Studies; D000069604:Dabigatran / Q000627:therapeutic use*; D057915:Drug Substitution; D065427:Factor Xa Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000069552:Rivaroxaban / Q000627:therapeutic use*; D013844:Thiazoles / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D011725:Pyridines; D013844:Thiazoles; D000069552:Rivaroxaban; D000069604:Dabigatran; C552171:edoxaban