title: Effects of age and sex on the single-dose pharmacokinetics and pharmacodynamics of apixaban.
abstract: OBJECTIVE
  The effects of age and sex on apixaban pharmacokinetics and pharmacodynamics were studied.
  
  
  METHODS
  This was an open-label, single-dose, 2 × 2 factorial study. Healthy young (aged 18-40 years) and elderly (aged ≥ 65 years) male and female subjects received a single oral 20 mg dose of apixaban. Blood and urine samples were collected for pharmacokinetic and pharmacodynamic (blood only) analyses. Subjects were monitored for adverse events throughout the study.
  
  
  RESULTS
  Seventy-nine subjects were enrolled into four groups: young males (n = 20), elderly males (n = 20), young females (n = 20) and elderly females (n = 19). Age did not affect the maximum observed plasma concentration (C max). The mean area under the concentration-time curve from time zero extrapolated to infinite time (AUC∞) was 32% greater in elderly subjects than in young subjects. The mean C max and AUC∞ values were 18 and 15% higher, respectively, in females than in males. The time course of the mean international normalized ratio (INR), modified prothrombin time (mPT) and anti-Xa activity tracked the apixaban concentration-time curve. All three pharmacodynamic measures exhibited a positive linear correlation with the plasma apixaban concentration. Differences in the mean INR, mPT and anti-Xa activity between age and sex groups were small (<15% at the maximum mean values) and were generally related to pharmacokinetic differences. However, anti-Xa activity demonstrated less variability than the INR or mPT, and may have utility as a bioassay for apixaban. Apixaban was well tolerated, with no serious adverse events.
  
  
  CONCLUSIONS
  There were no clinically meaningful age- or sex-related differences in the pharmacokinetics and pharmacodynamics of apixaban that would require dose modification on the basis of age or sex alone.
authors.affiliation: Discovery Medicine and Clinical Pharmacology, Bristol-Myers Squibb Research and Development, Mail Stop E12-16, Route 206 and Province Line Road, Princeton, NJ, 08543-4000, USA, charles.frost@bms.com.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Frost
authors.forename: Yan
authors.initials: Y
authors.lastname: Song
authors.forename: Andrew
authors.initials: A
authors.lastname: Shenker
authors.forename: Jessie
authors.initials: J
authors.lastname: Wang
authors.forename: Yu Chen
authors.initials: YC
authors.lastname: Barrett
authors.forename: Alan
authors.initials: A
authors.lastname: Schuster
authors.forename: Stuart I
authors.initials: SI
authors.lastname: Harris
authors.forename: Frank
authors.initials: F
authors.lastname: LaCreta
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D065427:Factor Xa Inhibitors / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D011720:Pyrazoles / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D011728:Pyridones / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D012044:Regression Analysis; D012737:Sex Factors; D055815:Young Adult
chemical_list: D065427:Factor Xa Inhibitors; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban