期刊
JOURNAL OF CLINICAL PHARMACOLOGY
卷 56, 期 5, 页码 637-645出版社
WILEY
DOI: 10.1002/jcph.633
关键词
anticoagulant; apixaban; renal impairment; pharmacokinetics; pharmacodynamics
资金
- Bristol-Myers Squibb
- Pfizer Inc.
- Bristol-Myers Squibb Company
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 15mL/min, compared with subjects with normal renal function), but it did not affect C-max 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.
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