Pharmacokinetics, pharmacodynamics, and safety of apixaban in subjects with end-stage renal disease on hemodialysis

J Clin Pharmacol. 2016 May;56(5):628-36. doi: 10.1002/jcph.628. Epub 2015 Dec 22.


An open-label, parallel-group, single-dose study was conducted to assess the pharmacokinetics, pharmacodynamics, and safety of apixaban in 8 subjects with end-stage renal disease (ESRD) on hemodialysis compared with 8 subjects with normal renal function. A single oral 5-mg dose of apixaban was administered once to healthy subjects and twice to subjects with ESRD, separated by ≥7 days: 2 hours before (on hemodialysis) and immediately after a 4-hour hemodialysis session (off hemodialysis). Blood samples were collected for determination of apixaban pharmacokinetic parameters, measures of clotting (prothrombin time, international normalized ratio, activated partial thromboplastin time), and anti-factor Xa (FXa) activity. Compared with healthy subjects, apixaban Cmax and AUCinf were 10% lower and 36% higher, respectively, in subjects with ESRD off hemodialysis. Hemodialysis in subjects with ESRD was associated with reductions in apixaban Cmax and AUCinf of 13% and 14%, respectively. The percent change from baseline in clotting measures was similar in healthy subjects and subjects with ESRD, and differences in anti-FXa activity were similar to differences in apixaban concentration. A single 5-mg oral dose of apixaban was well tolerated in both groups. In conclusion, ESRD resulted in a modest increase (36%) in apixaban AUC and no increase in Cmax , and hemodialysis had a limited impact on apixaban clearance.

Keywords: apixaban; end-stage renal disease; hemodialysis; pharmacodynamics; pharmacokinetics.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Area Under Curve
  • Factor Xa / analysis
  • Factor Xa Inhibitors* / adverse effects
  • Factor Xa Inhibitors* / blood
  • Factor Xa Inhibitors* / pharmacokinetics
  • Factor Xa Inhibitors* / pharmacology
  • Female
  • Humans
  • International Normalized Ratio
  • Kidney Failure, Chronic* / blood
  • Kidney Failure, Chronic* / metabolism
  • Kidney Failure, Chronic* / therapy
  • Male
  • Middle Aged
  • Partial Thromboplastin Time
  • Prothrombin Time
  • Pyrazoles* / adverse effects
  • Pyrazoles* / blood
  • Pyrazoles* / pharmacokinetics
  • Pyrazoles* / pharmacology
  • Pyridones* / adverse effects
  • Pyridones* / blood
  • Pyridones* / pharmacokinetics
  • Pyridones* / pharmacology
  • Renal Dialysis*


  • Factor Xa Inhibitors
  • Pyrazoles
  • Pyridones
  • apixaban
  • Factor Xa