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Influence of CYP3A polymorphisms on tacrolimus pharmacokinetics in kidney transplant recipients

The Pharmacogenomics Journal volume 21, pages 69–77 (2021)Cite this article

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A Correction to this article was published on 09 September 2020

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Abstract

Tacrolimus is characterized by a highly variable pharmacokinetics (PK) and a small therapeutic window. It is metabolized specifically by the CYP3A isoenzymes. This study aimed to determine, in kidney transplant patients, the influence of different genotypic clusters involving these SNPs CYP3A4*1B, CYP3A4*22, and CYP3A5*3 on Tacrolimus bioavailability during the first (PTP1) and the second (PTP2) posttransplant phase (PT). We included kidney transplant patients who received Tacrolimus and underwent drug monitoring by C0 monitoring. CYP3A4 and CYP3A5 genotyping were performed using PCR–RFLP. We classified the patients into four groups: Slow, Intermediate, rapid, and ultra-rapid metabolizers. We included 80 patients. The Tacrolimus dose-normalized C0 (C0/D ratio) was significantly decreased in intermediate, rapid, and ultra-rapid comparing with slow metabolisers. During PTP1 only CYP3A5*3 and CYP3A4*22 polymorphisms correlate significantly with C0/D ratio. Regardless of the PT phase and during the late one, only the CYP3A4 polymorphisms correlate significantly with the C0/D ratio. We identified that these SNPs are all associated independently with Tacrolimus exposure in different PT phases. Moreover, we are the first to define a genotypic cluster including the three CYP3A SNPs.

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Fig. 1: The variation of the C0/D ratio according to CYP3A4 and CYP3A5 alleles regardless of the posttransplant phase.
Fig. 2: The variation of the C0/D ratio according to CYP3A4 and CYP3A5 alleles during early and late of posttransplant phases.

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Change history

  • 07 September 2020

    The original version of this Article omitted the word “of” in the title and should have read “Influence of CYP3A polymorphisms on tacrolimus pharmacokinetics in kidney transplant recipients”. This has now been corrected in both the PDF and HTML versions of the Article.

  • 09 September 2020

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Authors and Affiliations

  1. Faculty of Sciences of Bizerte, Carthage University, Tunis, Tunisia

    Ibtissem Hannachi

  2. Laboratory of Pharmacology, Faculty of Medicine, University of Monastir, Monastir, Tunisia

    Ibtissem Hannachi, Zohra Chadli, Emna Kerkeni, Abdessalem Kolsi, Amel Chaabane, Nadia Ben Fredj, Naceur A. Boughattas & Karim Aouam

  3. Nephrology Department, University Hospital of Monastir, Monastir, Tunisia

    Mouna Hammouda

  4. Medical Chronobiology Unit, Fondation Rothschild, 75019, Paris, France

    Yvan Touitou

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Hannachi, I., Chadli, Z., Kerkeni, E. et al. Influence of CYP3A polymorphisms on tacrolimus pharmacokinetics in kidney transplant recipients. Pharmacogenomics J 21, 69–77 (2021). https://doi.org/10.1038/s41397-020-00179-4

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