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Erschienen in: Clinical Pharmacokinetics 5/2019

10.11.2018 | Review Article

Pharmacogenetics of Membrane Transporters of Tacrolimus in Solid Organ Transplantation

verfasst von: Camille Tron, Florian Lemaitre, Céline Verstuyft, Antoine Petitcollin, Marie-Clémence Verdier, Eric Bellissant

Erschienen in: Clinical Pharmacokinetics | Ausgabe 5/2019

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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.
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Metadaten
Titel
Pharmacogenetics of Membrane Transporters of Tacrolimus in Solid Organ Transplantation
verfasst von
Camille Tron
Florian Lemaitre
Céline Verstuyft
Antoine Petitcollin
Marie-Clémence Verdier
Eric Bellissant
Publikationsdatum
10.11.2018
Verlag
Springer International Publishing
Erschienen in
Clinical Pharmacokinetics / Ausgabe 5/2019
Print ISSN: 0312-5963
Elektronische ISSN: 1179-1926
DOI
https://doi.org/10.1007/s40262-018-0717-7

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