UNIGE document Scientific Article
previous document  unige:121245  next document
add to browser collection
Title

Phenotyping of human CYP450 enzymes by endobiotics: current knowledge and methodological approaches

Authors
Published in Clinical Pharmacokinetics. 2019
Abstract Drug response is subject to an important within- and between-individual variability owing, mainly, to pharmacokinetic and pharmacodynamic factors. Pharmacokinetics includes metabolism by cytochrome P450 (CYP450), major enzymes of phase I reactions that are responsible for the biotransformation of around 60% of the currently approved drugs. CYP450 activity and/or expression are influenced by multiple intrinsic and extrinsic factors, such as drug-drug interactions or genetic polymorphisms. Present phenotyping strategies with xenobiotics used to assess CYP450 activity could be replaced by less invasive procedures using endogenous CYP450 biomarkers. In this work, we review existing knowledge on endobiotics and their ability to characterise variability of the CYP1A2, CYP2C19, CYP2D6 and CYP3A enzymes in humans. To date, it appears that there is a lack of clinical data for the majority of the endogenous compounds described in the literature or some important limitations to allow their use in clinical practice. Additional studies are needed to fill the gap or to identify new candidates, in particular through the use of metabolomics. The use of multivariate models is also a very promising approach to enhance prediction by combining several endogenous phenotyping metrics and other covariates.
Identifiers
PMID: 31131437
Full text
Article (Published version) (1.1 MB) - document accessible for UNIGE members only Limited access to UNIGE
Structures
Research groups Pharmaco-omiques et médecine de précision (1003)
Groupe Desmeules Jules (pharmacologie/toxicologie) (567)
Citation
(ISO format)
MAGLIOCCO, Gaëlle et al. Phenotyping of human CYP450 enzymes by endobiotics: current knowledge and methodological approaches. In: Clinical Pharmacokinetics, 2019. doi: 10.1007/s40262-019-00783-z https://archive-ouverte.unige.ch/unige:121245

136 hits

2 downloads

Update

Deposited on : 2019-07-24

Export document
Format :
Citation style :