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Pharmacokinetics, pharmacodynamics, and safety of apixaban in subjects with end‐stage renal disease on hemodialysis
Author(s) -
Wang Xiaoli,
Tirucherai Giridhar,
Marbury Thomas C.,
Wang Jessie,
Chang Ming,
Zhang Donglu,
Song Yan,
Pursley Janice,
Boyd Rebecca A.,
Frost Charles
Publication year - 2016
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.628
Subject(s) - apixaban , cmax , hemodialysis , medicine , end stage renal disease , pharmacokinetics , partial thromboplastin time , pharmacodynamics , renal function , pharmacology , urology , gastroenterology , coagulation , warfarin , rivaroxaban , atrial fibrillation
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 C max and AUC inf were 10% lower and 36% higher, respectively, in subjects with ESRD off hemodialysis. Hemodialysis in subjects with ESRD was associated with reductions in apixaban C max and AUC inf 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 C max , and hemodialysis had a limited impact on apixaban clearance.