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Pharmacogenetics of Membrane Transporters of Tacrolimus in Solid Organ Transplantation

  • Camille Tron
  • Florian Lemaitre
  • Céline Verstuyft
  • Antoine Petitcollin
  • Marie-Clémence Verdier
  • Eric Bellissant
Review Article

Abstract

Membrane transporters play an essential role in the pharmacokinetics of drugs as they mediate exchanges between biological compartments. Tacrolimus is characterized by wide interpatient variability in terms of its pharmacokinetics that may in part be due to genetic factors. The pharmacogenetics of drug transporters is therefore a promising area to explore in the clinical pharmacology of tacrolimus. The aim of this review is to provide an overview of currently available data regarding the pharmacogenetics of membrane transporters that may be involved in the interindividual variability of the response to tacrolimus. Several genetic variants in genes coding for influx or efflux membrane transporters (e.g. ABCB1, ABCC2, ABCC8, SLC30A8, SLCO1B1/3, SLC28A1, SLC22A11, and SLC28A3) have been associated with tacrolimus pharmacokinetics variability or the occurrence of toxicity; however, there is still a degree of controversy as to the impact of these variants in vivo and further investigations are needed to confirm these results in larger cohorts and to validate the relevance of such genetic biomarkers for personalization of immunosuppressive therapy in solid organ transplantations. The relationship between transporter polymorphisms and the intracellular concentration of tacrolimus should also be further investigated. Finally, the main challenge could be elucidation of the interplay of biological mechanisms underlying genetic variations that alter the drug concentration or its clinical effect.

Notes

Author contributions

CT wrote the manuscript, and FL, CV, AP, MCV, and EB fully reviewed the manuscript.

Compliance with Ethical Standards

Funding

No sources of funding were used to assist in the preparation of this review.

Conflict of interest

Camille Tron, Florian Lemaitre, Céline Verstuyft, Antoine Petitcollin, Marie-Clémence Verdier, and Eric Bellissant have no conflicts of interest to declare that are relevant to the content of this review.

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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Department of Clinical and Biological Pharmacology and Pharmacovigilance, Pharmacoepidemiology and Drug Information CentreRennes University HospitalRennesFrance
  2. 2.Laboratory of Experimental and Clinical Pharmacology, Faculty of MedicineRennes 1 UniversityRennesFrance
  3. 3.Clinical Investigation Centre, CIC-P Inserm 1414RennesFrance
  4. 4.Department of Molecular Genetics, Pharmacogenetics, and HormonologyHôpital Bicêtre, Groupe Hospitalier Paris Sud, AP-HPLe Kremlin BicêtreFrance
  5. 5.INSERM UMR1178, Team (Depression and Antidepressants), Faculty of Medicine Paris-SudParis-Sud UniversityLe Kremlin BicêtreFrance

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