A single 10-mg dose of apixaban increased AUC∞ by 44% in subjects with severe renal impairment (CLcr 15 mL/min) compared to normal renal function, suggesting dose adjustment is not required.
Does renal impairment affect the pharmacokinetics, pharmacodynamics, and safety of a single 10-mg oral dose of apixaban?
Renal impairment modestly increases apixaban exposure but does not alter its pharmacodynamic profile, suggesting dose adjustment is not required based solely on renal function.
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.
Chang et al. (Fri,) conducted a other in Renal impairment. Apixaban vs. Healthy subjects was evaluated on Relationship between apixaban AUC∞ and 24-hour creatinine clearance (CLcr). A single 10-mg dose of apixaban increased AUC∞ by 44% in subjects with severe renal impairment (CLcr 15 mL/min) compared to normal renal function, suggesting dose adjustment is not required.