title: Single- and multiple-dose pharmacokinetics, pharmacodynamics, and safety of apixaban in healthy Chinese subjects.
abstract: BACKGROUND
  The pharmacokinetics (PK), pharmacodynamics (PD), and safety of apixaban were assessed in healthy Chinese subjects in this randomized, placebo-controlled, double-blind, single-sequence, single- and multiple-dose study.
  
  
  METHODS
  Eighteen subjects 18-45 years of age were randomly assigned (2:1 ratio) to receive apixaban or matched placebo. Subjects received a single 10 mg dose of apixaban or placebo on day 1, followed by 10 mg apixaban or placebo twice daily for 6 days (days 4-9). The PK and PD of apixaban were assessed by collecting plasma samples for 72 hours following the dose on day 1 and the morning dose on day 9, and measuring apixaban concentration and anti-Xa activity. Safety was assessed via physical examinations, vital sign measurements, electrocardiograms, and clinical laboratory evaluations.
  
  
  RESULTS
  PK analysis showed similar characteristics of apixaban after single and multiple doses, including a median time to maximum concentration of ~3 hours, mean elimination half-life of ~11 hours, and renal clearance of ~1.2 L/hour. The accumulation index was 1.7, consistent with twice-daily dosing and the observed elimination half-life. Single-dose data predict multiple-dose PK, therefore apixaban PK are time-independent. The relationship between anti-Xa activity and plasma apixaban concentrations appears to be linear. Apixaban was safe and well tolerated, with no bleeding-related adverse events reported.
  
  
  CONCLUSIONS
  Apixaban was safe and well tolerated in healthy Chinese subjects. Apixaban PK and PD were predictable and consistent with findings from previous studies in Asian and non-Asian subjects. The administration of apixaban does not require any dose modification based on race.
authors.affiliation: Peking University First Hospital, Beijing, People's Republic of China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Song
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Jessie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Schuster
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Yu Chen
authors.initials: YC
authors.lastname: Barrett
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Frost
keywords: apixaban; factor Xa inhibitor; oral anticoagulant; pharmacodynamics; pharmacokinetics