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Regenerative Medicine

CYP3A5 and ABCB1 polymorphisms influence tacrolimus concentrations in peripheral blood mononuclear cells after renal transplantation

    Arnaud Capron

    Department of Clinical Chemistry, Laboratory of Toxicology & Therapeutic Drug Monitoring, Cliniques universitaires St Luc, Université Catholique de Louvain, 10 Hippocrate Ave, B-1200 Brussels, Belgium

    Louvain centre for Toxicology & Applied Pharmacology, Cliniques universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium

    ,
    Michel Mourad

    Abdominal Transplantation Unit, Cliniques universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium

    ,
    Martine De Meyer

    Abdominal Transplantation Unit, Cliniques universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium

    ,
    Luc De Pauw

    Abdominal Transplantation Unit, Cliniques universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium

    ,
    Djamila Chaib Eddour

    Abdominal Transplantation Unit, Cliniques universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium

    ,
    Dominique Latinne

    Immuno-haematology Department, Cliniques universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium.

    ,
    Laure Elens

    Louvain centre for Toxicology & Applied Pharmacology, Cliniques universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium

    ,
    Vincent Haufroid

    Department of Clinical Chemistry, Laboratory of Toxicology & Therapeutic Drug Monitoring, Cliniques universitaires St Luc, Université Catholique de Louvain, 10 Hippocrate Ave, B-1200 Brussels, Belgium

    Louvain centre for Toxicology & Applied Pharmacology, Cliniques universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium

    &
    Published Online:https://doi.org/10.2217/pgs.10.43

    Aims: This prospective study investigated the effect of genetic polymorphisms in a biotransformation enzyme (CYP3A5) and a transporter protein (ABCB1) on tacrolimus (Tac) whole blood concentrations in renal transplantation, and more specifically on peripheral blood mononuclear cell (PBMC) drug concentrations, after renal transplantation. Materials & methods: A total of 96 renal transplant recipients were genotyped for the exon 11 (1199G>A), 21 (3435C>T) and 26 (2677G>T/A) polymorphisms in the ABCB1 gene and for the intron 3 polymorphism in the CYP3A5 gene. Tac blood and PBMC concentrations were determined at day 7 after transplantation and at steady state, and then compared with recipient genotypes. Results & conclusion: The ABCB1 1199G>A, 3435C>T and 2677G>T/A SNPs, appeared to reduce the activity of P-glycoprotein towards Tac, increasing Tac PBMC concentrations. The impact of ABCB1 genetic polymorphisms on Tac blood concentrations was negligible. As increased Tac intracellular concentrations might in turn enhance immunosuppressive status and prevention or rejection, ABCB1 recipient genotyping might be useful to better individualize the Tac immunosuppressive therapy in renal transplantation.

    Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

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