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Br J Clin Pharmacol. 2010 Nov;70(5):703-12. doi: 10.1111/j.1365-2125.2010.03753.x.

Effects of renal impairment on the pharmacokinetics, pharmacodynamics and safety of rivaroxaban, an oral, direct Factor Xa inhibitor.

Author information

1
Clinical Pharmacology, Bayer Schering Pharma AG, 42096 Wuppertal, Germany. dagmar.kubitza@bayerhealthcare.com

Abstract

AIM:

This study evaluated the effects of impaired renal function on the pharmacokinetics, pharmacodynamics and safety of rivaroxaban (10mg single dose), an oral, direct Factor Xa inhibitor.

METHODS:

Subjects (n= 32) were stratified based on measured creatinine clearance: healthy controls (≥80ml min(-1) ), mild (50-79mlmin(-1) ), moderate (30-49mlmin(-1) ) and severe impairment (<30mlmin(-1) ).

RESULTS:

Renal clearance of rivaroxaban decreased with increasing renal impairment. Thus, plasma concentrations increased and area under the plasma concentration-time curve (AUC) LS-mean values were 1.44-fold (90% confidence interval [CI] 1.1, 1.9; mild), 1.52-fold (90% CI 1.2, 2.0; moderate) and 1.64-fold (90% CI 1.2, 2.2; severe impairment) higher than in healthy controls. Corresponding values for the LS-mean of the AUC for prolongation of prothrombin time were 1.33-fold (90% CI 0.92, 1.92; mild), 2.16-fold (90% CI 1.51, 3.10 moderate) and 2.44-fold (90% CI 1.70, 3.49 severe) higher than in healthy subjects, respectively. Likewise, the LS-mean of the AUC for Factor Xa inhibition in subjects with mild renal impairment was 1.50-fold (90% CI 1.07, 2.10) higher than in healthy subjects. In subjects with moderate and severe renal impairment, the increase was 1.86-fold (90% CI 1.34, 2.59) and 2.0-fold (90% CI 1.44, 2.78) higher than in healthy subjects, respectively.

CONCLUSIONS:

Rivaroxaban clearance is decreased with increasing renal impairment, leading to increased plasma exposure and pharmacodynamic effects, as expected for a partially renally excreted drug. However, the influence of renal function on rivaroxaban clearance was moderate, even in subjects with severe renal impairment.

PMID:
21039764
PMCID:
PMC2997310
DOI:
10.1111/j.1365-2125.2010.03753.x
[Indexed for MEDLINE]
Free PMC Article
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