Effect of ABCB1 Gene Carriage and Drug-Drug Interactions on Apixaban and Rivaroxaban Pharmacokinetics and Clinical Outcomes in Patients with Atrial Fibrillation and Deep Vein Thrombosis

Abstract

Aim. To investigate the effect of ABCB1 gene carriage and interdrug interactions on apixaban pharmacokinetics and clinical outcomes in patients with atrial fibrillation and deep vein thrombosis.Material and methods. Patients hospitalized at Yudin State Clinical Hospital participated in the study. A total of 92 patients (50 patients received apixaban and 42 – rivaroxaban) with non-valvular atrial fibrillation and deep vein thrombosis were included. Genotyping was performed by real-time polymerase chain reaction. Direct oral anticoagulants concentrations were measured using an electrospray ionization mass spectrometer in positive ionization mode.Results. In our study we found that in patients carrying the CT+TT ABCB1 (rs4148738) C>T genotype encoding the carrier protein (P-gp), the plasma concentration of rivaroxaban was statistically significantly higher p= 0.026. In addition, we found that patients taking apixaban together with a CYP3A4/P-gp inhibitor were 3.5 times more likely to have hemorrhagic complications than those without inhibitors p = 0.004.Conclusion. Our study revealed that the plasma concentration of rivaroxaban was higher in patients carrying the ABCB1 (rs4148738) C>T polymorphism T allele. And patients taking apixaban together with CYP3A4/P-gp inhibitor had higher risk of hemorrhagic complications in comparison with patients not taking such drugs. Further studies are needed on the influence of pharmacogenetics and pharmacokinetics on the safety and efficacy profile of apixaban and rivaroxaban, taking into account the trend of systemic approach to optimization of anticoagulant therapy of direct oral anticoagulants based on pharmacokinetic, pharmacogenetic biomarkers.