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 admin...

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Bibliographic Details
Published in:Journal of clinical pharmacology Vol. 56; no. 5; pp. 628 - 636
Main Authors: Wang, Xiaoli, Tirucherai, Giridhar, Marbury, Thomas C., Wang, Jessie, Chang, Ming, Zhang, Donglu, Song, Yan, Pursley, Janice, Boyd, Rebecca A., Frost, Charles
Format: Journal Article
Language:English
Published: England Blackwell Publishing Ltd 01.05.2016
American College of Clinical Pharmacology
Wiley Subscription Services, Inc
Subjects:
Adult
apixaban
Area Under Curve
end-stage renal disease
Factor Xa - analysis
Factor Xa Inhibitors - adverse effects
Factor Xa Inhibitors - blood
Factor Xa Inhibitors - pharmacokinetics
Factor Xa Inhibitors - pharmacology
Female
Hemodialysis
Humans
International Normalized Ratio
Kidney diseases
Kidney Failure, Chronic - blood
Kidney Failure, Chronic - metabolism
Kidney Failure, Chronic - therapy
Male
Medicare
Middle Aged
Partial Thromboplastin Time
pharmacodynamics
pharmacokinetics
Prothrombin Time
Pyrazoles - adverse effects
Pyrazoles - blood
Pyrazoles - pharmacokinetics
Pyrazoles - pharmacology
Pyridones - adverse effects
Pyridones - blood
Pyridones - pharmacokinetics
Pyridones - pharmacology
Renal Dialysis
hemodialysis
pharmacokinetics
end-stage renal disease
apixaban
pharmacodynamics
ISSN:0091-2700, 1552-4604, 1552-4604
Online Access:Get full text
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Summary: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.
Bibliography:Bristol-Myers Squibb
Pfizer Inc.
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ArticleID:JCPH628
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SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:0091-2700
1552-4604
1552-4604
DOI:10.1002/jcph.628