PMID- 27121940
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160429
LR  - 20220331
IS  - 2160-763X (Print)
IS  - 2160-763X (Linking)
VI  - 2
IP  - 4
DP  - 2013 Oct
TI  - Bioavailability and Safety of the Factor Xa Inhibitor Edoxaban and the Effects of 
      Quinidine in Healthy Subjects.
PG  - 358-66
LID - 10.1002/cpdd.53 [doi]
AB  - BACKGROUND: Edoxaban is an oral, once-daily, direct factor Xa inhibitor under 
      investigation for stroke prevention in patients with atrial fibrillation and for 
      treatment and secondary prevention of venous thromboembolism. This study 
      evaluated edoxaban absolute bioavailability and effects of the P-glycoprotein 
      inhibitor quinidine on edoxaban pharmacokinetics after intravenous edoxaban 
      administration. METHODS: Healthy volunteers received three treatments in a 
      randomized sequence: single oral 60-mg edoxaban dose, single intravenous 30-mg 
      edoxaban dose, and concomitant single intravenous 30-mg edoxaban dose with 
      quinidine 300 mg every 8 hours for 4 days. The primary objective was to determine 
      absolute bioavailability of edoxaban. Secondary objectives included 
      pharmacokinetics and pharmacodynamics of edoxaban after oral or intravenous 
      administration, quinidine effect on intravenous edoxaban pharmacokinetics, and 
      safety. RESULTS: Thirty-six subjects were randomized; five discontinued (three 
      for adverse events [AEs]). Edoxaban oral absolute bioavailability was 61.8%. With 
      concomitant quinidine, total edoxaban exposure increased  approximately 35% and total clearance 
      decreased  approximately 25%. Coagulation parameters increased after edoxaban administration in 
      most subjects, but returned to baseline within 24 hours postdose. No deaths, 
      serious AEs, or bleeding-related AEs occurred. CONCLUSIONS: Absolute 
      bioavailability of edoxaban in healthy volunteers was established (61.8%). 
      Edoxaban, administered orally or intravenously, appeared to be safe and well 
      tolerated.
CI  - (c) 2013, The American College of Clinical Pharmacology.
FAU - Matsushima, Nobuko
AU  - Matsushima N
AD  - Daiichi Sankyo Co., Ltd., Tokyo, Japan.
FAU - Lee, Frank
AU  - Lee F
AD  - Celerion, Inc., Neptune, NJ, USA.
FAU - Sato, Toshiyuki
AU  - Sato T
AD  - Daiichi Sankyo Pharma Development, Edison, NJ, USA.
FAU - Weiss, Daniel
AU  - Weiss D
AD  - Celerion, Inc., Neptune, NJ, USA.
FAU - Mendell, Jeanne
AU  - Mendell J
AD  - Daiichi Sankyo Pharma Development, Edison, NJ, USA.
LA  - eng
PT  - Journal Article
DEP - 20130909
PL  - United States
TA  - Clin Pharmacol Drug Dev
JT  - Clinical pharmacology in drug development
JID - 101572899
OTO - NOTNLM
OT  - bioavailability
OT  - edoxaban
OT  - factor Xa
OT  - pharmacokinetics
OT  - quinidine
EDAT- 2013/10/01 00:00
MHDA- 2013/10/01 00:01
CRDT- 2016/04/29 06:00
PHST- 2012/10/11 00:00 [received]
PHST- 2013/07/12 00:00 [accepted]
PHST- 2016/04/29 06:00 [entrez]
PHST- 2013/10/01 00:00 [pubmed]
PHST- 2013/10/01 00:01 [medline]
AID - 10.1002/cpdd.53 [doi]
PST - ppublish
SO  - Clin Pharmacol Drug Dev. 2013 Oct;2(4):358-66. doi: 10.1002/cpdd.53. Epub 2013 
      Sep 9.