4.7 Article

CYP3A5Gene-Guided Tacrolimus Treatment of Living-Donor Egyptian Kidney Transplanted Patients

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FRONTIERS IN PHARMACOLOGY
卷 11, 期 -, 页码 -

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FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2020.01218

关键词

kidney transplantation; living donor; tacrolimus; Egyptian population; dose requirements; C; D ratio; tacrolimus blood levels

资金

  1. National Research Infrastructure on Integrated Structural Biology, Drug Screening Efforts and Drug target functional characterization (INSPIRED) [MIS 5002550]

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Background Tacrolimus is an approved first-line immunosuppressive agent for kidney transplantations. Part of interindividual and interethnic differences in the response of patients to tacrolimus is attributed to polymorphisms at CYP3A5 metabolic enzyme.CYP3A5gene expression status is associated with tacrolimus dose requirement in renal transplant recipients. Materials and Methods In this study, we determined the allelic frequency ofCYP3A5*3in 76 renal transplanted patients of Egyptian descent. Secondly, we evaluated the influence of theCYP3A5gene variant on tacrolimus doses required for these patients as well on dose-adjusted tacrolimus trough-concentrations. Results TheCYP3A5*3variant was the most frequent allele detected at 85.53%. Additionally, our results showed that, mean tacrolimus daily requirements for heterozygous patients (CYP3A5*1/*3) were significantly higher compared to homozygous patients (CYP3A5*3/*3) during the first year after kidney transplantation. Conclusion This is the first study in Egypt contributing to the individualization of tacrolimus dosing in Egyptian patients, informed by theCYP3A5genotype.

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