A single 5-mg dose of apixaban in subjects with ESRD resulted in a 36% higher AUCinf and 10% lower Cmax compared with healthy subjects, and hemodialysis had limited impact on clearance.
How do the pharmacokinetics, pharmacodynamics, and safety of a single 5-mg dose of apixaban compare between subjects with ESRD on hemodialysis and healthy subjects?
In subjects with ESRD on hemodialysis, a single 5-mg dose of apixaban results in a modest increase in exposure (AUC) without an increase in Cmax, and hemodialysis has limited impact on its clearance.
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.
Wang et al. (Wed,) conducted a other in End-stage renal disease on hemodialysis (n=16). Apixaban vs. Healthy subjects with normal renal function was evaluated on Pharmacokinetics (Cmax, AUCinf), pharmacodynamics, and safety. A single 5-mg dose of apixaban in subjects with ESRD resulted in a 36% higher AUCinf and 10% lower Cmax compared with healthy subjects, and hemodialysis had limited impact on clearance.