Pharmacokinetics, pharmacodynamics, and safety of apixaban in subjects with end-stage renal disease on hemodialysis.
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.
At time of research, Bristol-Myers Squibb, Princeton, NJ, USA.
Xiaoli
X
Wang
At time of research, Bristol-Myers Squibb, Princeton, NJ, USA.
Giridhar
G
Tirucherai
Orlando Clinical Research Center, Orlando, FL, USA.
Thomas C
TC
Marbury
At time of research, Bristol-Myers Squibb, Princeton, NJ, USA.
Jessie
J
Wang
At time of research, Bristol-Myers Squibb, Princeton, NJ, USA.
Ming
M
Chang
At time of research, Bristol-Myers Squibb, Princeton, NJ, USA.
Donglu
D
Zhang
At time of research, Bristol-Myers Squibb, Princeton, NJ, USA.
Yan
Y
Song
At time of research, Bristol-Myers Squibb, Princeton, NJ, USA.
Janice
J
Pursley
Pfizer Inc, Groton, CT, USA.
Rebecca A
RA
Boyd
At time of research, Bristol-Myers Squibb, Princeton, NJ, USA.
Charles
C
Frost
D000328:Adult; D019540:Area Under Curve; D015951:Factor Xa / Q000032:analysis; D065427:Factor Xa Inhibitors / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D007676:Kidney Failure, Chronic / Q000097:blood / Q000378:metabolism / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D011517:Prothrombin Time; D011720:Pyrazoles / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D011728:Pyridones / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D006435:Renal Dialysis
D065427:Factor Xa Inhibitors; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D015951:Factor Xa
apixaban; end-stage renal disease; hemodialysis; pharmacodynamics; pharmacokinetics