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J Clin Pharmacol. 2016 May;56(5):637-45. doi: 10.1002/jcph.633. Epub 2015 Dec 4.

Effect of renal impairment on the pharmacokinetics, pharmacodynamics, and safety of apixaban.

Author information

1
At the time of research, Bristol-Myers Squibb, Princeton, NJ, USA.
2
Global Innovative Pharma Business Clinical Pharmacology, Pfizer Inc., Groton, CT, USA.

Abstract

This open-label study evaluated apixaban pharmacokinetics, pharmacodynamics, and safety in subjects with mild, moderate, or severe renal impairment and in healthy subjects following a single 10-mg oral dose. The primary analysis determined the relationship between apixaban AUC∞ and 24-hour creatinine clearance (CLcr ) as a measure of renal function. The relationships between 24-hour CLcr and iohexol clearance, estimated CLcr (Cockcroft-Gault equation), and estimated glomerular filtration rate (modification of diet in renal disease [MDRD] equation) were also assessed. Secondary objectives included assessment of safety and tolerability as well as international normalized ratio (INR) and anti-factor Xa activity as pharmacodynamic endpoints. The regression analysis showed that decreasing renal function resulted in modestly increased apixaban exposure (AUC∞ increased by 44% in severe impairment with a 24-hour CLcr of 15 mL/min, compared with subjects with normal renal function), but it did not affect Cmax or the direct relationship between apixaban plasma concentration and anti-factor Xa activity or INR. The assessment of renal function measured by iohexol clearance, Cockcroft-Gault, and MDRD was consistent with that determined by 24-hour CLcr . Apixaban was well tolerated in this study. These results suggest that dose adjustment of apixaban is not required on the basis of renal function alone.

KEYWORDS:

anticoagulant; apixaban; pharmacodynamics; pharmacokinetics; renal impairment

PMID:
26358690
DOI:
10.1002/jcph.633
[Indexed for MEDLINE]

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