Is Eliquis Bound to Albumin?
Yes, Eliquis (apixaban) is highly bound to albumin, with plasma protein binding of approximately 87% in humans, primarily to albumin. 1
Protein Binding Characteristics
Apixaban demonstrates 92-94% protein binding according to KDIGO guidelines, which is consistent with the FDA label data showing approximately 87% plasma protein binding. 2, 1 This high degree of albumin binding places apixaban in the category of "heavily albumin-bound" direct oral anticoagulants.
Comparative Protein Binding Among DOACs
The extent of apixaban's protein binding is similar to other factor Xa inhibitors but differs significantly from direct thrombin inhibitors:
- Apixaban: 87-94% protein bound (primarily albumin) 2, 1
- Rivaroxaban: 92-95% protein bound (mainly albumin) 2
- Edoxaban: 55% protein bound 2
- Dabigatran: 35% protein bound 2
Clinical Implications of High Albumin Binding
Impact on Drug Distribution and Half-Life
The high protein binding of apixaban results in a volume of distribution (Vss) of approximately 21 liters, which is relatively limited compared to less protein-bound agents. 1 This extensive albumin binding contributes to apixaban's half-life of approximately 12 hours following oral administration. 1, 3
Hypoalbuminemia Considerations
KDIGO guidelines specifically warn that the effects of hypoalbuminemia on apixaban dosing have not been studied, and the heavy albumin binding is likely to substantially affect drug half-lives in patients with low albumin levels. 2 This is particularly relevant in:
- Nephrotic syndrome patients where fluctuating serum albumin levels may alter free drug concentrations 2
- Patients with liver dysfunction where albumin synthesis may be impaired 1
- Critically ill or malnourished patients with reduced albumin levels 2
Renal Clearance Despite Protein Binding
Despite the high protein binding, approximately 27% of apixaban's total clearance occurs via renal excretion, with the remainder eliminated through metabolism, biliary excretion, and direct intestinal excretion. 1, 3 This relatively low renal clearance compared to other DOACs (rivaroxaban 66%, edoxaban 50%) makes apixaban potentially preferable in patients with renal impairment. 2, 4
Important Clinical Caveats
The high albumin binding means that in conditions with fluctuating or low albumin levels, free (active) drug concentrations may vary unpredictably, even when total drug levels remain stable. 2 This is particularly problematic because:
- Routine coagulation tests (PT, aPTT) are not reliable for monitoring apixaban's anticoagulant effect 1
- No validated assay exists for routine clinical monitoring of apixaban levels 1
- Dose adjustments based on albumin levels are not established in clinical guidelines 2
KDIGO guidelines recommend that until pharmacokinetic studies are performed in patients with hypoalbuminemia, warfarin remains the anticoagulant of choice in nephrotic syndrome due to long-term experience and the ability to monitor INR, despite warfarin also being protein-bound. 2