Mahieu Gwenaëlle, Sennesael Anne-Laure, Pochet Lionel, Haufroid Vincent, Van Bambeke Françoise, Spinewine Anne, Elens Laure
Pharmacologie Cellulaire et Moléculaire, Louvain Drug Research Institute (LDRI), Université catholique de Louvain (UCLouvain), Brussels, Belgium.
Integrated PharmacoMetrics, PharmacoGenomics and Pharmacokinetics (PMGK) Research Group, Louvain Drug Research Institute (LDRI), Université catholique de Louvain (UCLouvain), Brussels, Belgium.
Res Pract Thromb Haemost. 2024 Jul 22;8(5):102521. doi: 10.1016/j.rpth.2024.102521. eCollection 2024 Jul.
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.
To determine the effect of tacrolimus on ABCB1-mediated rivaroxaban transport in order to support clinician practice.
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.
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.
Our study does not provide evidence for a possible interaction between tacrolimus and rivaroxaban when used together in practice.
在肺移植患者中，直接口服抗凝剂常与他克莫司等免疫抑制药物联合使用。由于他克莫司是外排蛋白ABCB1的底物和抑制剂，而ABCB1也转运直接口服抗凝剂，因此需要研究由竞争该转运蛋白介导的潜在药物相互作用。
确定他克莫司对ABCB1介导的利伐沙班转运的影响，以支持临床医生的实践。
通过稳定转染过程生成基于人胚肾293细胞的重组细胞系模型，以过表达ABCB1或不表达（对照细胞）。通过积累实验评估他克莫司对ABCB1介导的利伐沙班转运的影响。
与对照细胞相比，在各自的临床相关浓度下，ABCB1的表达降低了利伐沙班和他克莫司的细胞内积累。这证实了ABCB1参与了他克莫司和利伐沙班的主动转运。然而，在这些临床相关浓度下，他克莫司对利伐沙班的处置没有显著影响。
我们的研究没有提供他克莫司和利伐沙班在实际联合使用时可能存在相互作用的证据。
