ABCB1
HEK293 cells
anticoagulants
drug interactions
lung transplantation
rivaroxaban
tacrolimus
Journal
Research and practice in thrombosis and haemostasis
ISSN: 2475-0379
Titre abrégé: Res Pract Thromb Haemost
Pays: United States
ID NLM: 101703775
Informations de publication
Date de publication:
Jul 2024
Jul 2024
Historique:
received:
24
02
2024
revised:
04
07
2024
accepted:
09
07
2024
medline:
4
9
2024
pubmed:
4
9
2024
entrez:
4
9
2024
Statut:
epublish
Résumé
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 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.
Sections du résumé
Background
UNASSIGNED
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
UNASSIGNED
To determine the
Methods
UNASSIGNED
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
UNASSIGNED
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
UNASSIGNED
Our study does not provide evidence for a possible interaction between tacrolimus and rivaroxaban when used together in practice.
Identifiants
pubmed: 39228433
doi: 10.1016/j.rpth.2024.102521
pii: S2475-0379(24)00216-4
pmc: PMC11369460
doi:
Types de publication
Journal Article
Langues
eng
Pagination
102521Informations de copyright
© 2024 The Authors.