Genetic variations of the xenoreceptors NR1I2 and NR1I3 and their effect on drug disposition and response variability

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Genetic variations of the xenoreceptors NR1I2 and NR1I3 and their effect on drug disposition and response variability

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Mbatchi, Litaty Céphanoée | Brouillet, Jean-Paul | Evrard, Alexandre

International audience. NR1I2 (PXR) and NR1I3 (CAR) are nuclear receptors that are classified as xenoreceptors. Upon activation by various xenobiotics, including marketed drugs, they regulate the transcription level of major drug-metabolizing enzymes and transporters and facilitate the elimination of xenobiotics from the body. The modulation of the activity of these two xenoreceptors by various ligands is a major source of pharmacokinetic variability of environmental origin. NR1I2 and NR1I3 genetic polymorphisms can affect the pharmacokinetics and therapeutic response to many drugs, such as irinotecan, tacrolimus and atazanavir. This review provides an overview of NR1I2 and NR1I3 pharmacogenetic studies in various therapeutic fields (oncology, immunomodulation and infectiology) and discusses the implementation of NR1I2 and NR1I3 genetic polymorphism testing in the clinical routine.

Langue: en

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