Reusing Blood Samples from a Hospital-based Cohort to Apixaban Plasma Concentrations.

Area of Science:

• Pharmacology
• Clinical Pharmacy
• Drug Metabolism

Background:

• Apixaban is a widely used oral anticoagulant for atrial fibrillation.
• Apixaban metabolism involves cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) efflux.
• Previous studies linked CYP3A4/P-gp inhibitors (amiodarone, diltiazem) to increased bleeding risk in apixaban users.

Purpose of the Study:

• To test the hypothesis that concomitant CYP3A4/P-gp inhibitors increase apixaban plasma concentrations.
• To evaluate the feasibility of using biobanked samples for pharmacokinetic studies.

Main Methods:

• Analysis of plasma samples from patients on apixaban, comparing those also taking CYP3A4/P-gp inhibitors versus those who were not.
• Utilized the BioVU biobank, linking de-identified electronic medical records with plasma samples.
• Measured apixaban concentrations using a chromogenic anti-Xa assay.

Main Results:

• Patients taking concomitant CYP3A4/P-gp inhibitors had significantly higher apixaban plasma concentrations (347±64 ng/mL) compared to controls (166±67 ng/mL).
• No significant differences in age, weight, or serum creatinine were observed between groups.
• Demonstrated the practicality of using biobanked samples for pharmacokinetic research.

Conclusions:

• Pilot study results support the hypothesis that CYP3A4/P-gp inhibitors increase apixaban levels.
• Higher apixaban concentrations may explain the increased bleeding risk observed with these drug combinations.
• This biobanking approach is effective for pharmacokinetic research in large patient cohorts.