In vitro assessment of the risk of ABCB1-mediated drug–drug interaction between rivaroxaban and tacrolimus in human embryonic kidney 293 recombinant cell lines

Background

In lung transplant patients, direct oral anticoagulants are often taken in combination with immunosuppressive drugs such as tacrolimus. Since tacrolimus is a substrate and inhibitor of the efflux protein ABCB1, also transporting direct oral anticoagulants, a possible drug–drug interaction mediated by competition for this transporter needs to be investigated.

Objectives

To determine the in vitro effect of tacrolimus on ABCB1-mediated rivaroxaban transport in order to support clinician practice.

Methods

Recombinant cell line models, based on human embryonic kidney 293 cells, were generated by a stable transfection process to overexpress ABCB1 or not (control cells). The impact of tacrolimus on ABCB1-mediated rivaroxaban transport was assessed by accumulation experiments.

Results

ABCB1 expression decreased the cellular accumulation of rivaroxaban and tacrolimus at their respective clinically relevant concentrations when compared with control cells. This confirms the involvement of ABCB1 in the active transport of tacrolimus and rivaroxaban. However, tacrolimus had no significant influence on rivaroxaban disposition at those clinically relevant concentrations.

Conclusion

Our study does not provide evidence for a possible interaction between tacrolimus and rivaroxaban when used together in practice.