Format

Send to

Choose Destination
Clin Pharmacokinet. 2019 May 27. doi: 10.1007/s40262-019-00783-z. [Epub ahead of print]

Phenotyping of Human CYP450 Enzymes by Endobiotics: Current Knowledge and Methodological Approaches.

Magliocco G1,2, Thomas A3,4,5, Desmeules J1,2,4,6, Daali Y7,8,9,10.

Author information

1
Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205, Geneva, Switzerland.
2
Geneva-Lausanne School of Pharmacy, University of Geneva, Geneva, Switzerland.
3
Unit of Toxicology, CURML, Lausanne-Geneva, Switzerland.
4
Swiss Center for Applied Human Toxicology, Geneva, Switzerland.
5
Faculty of Biology and Medicine, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
6
Faculty of Medicine, University of Geneva, Geneva, Switzerland.
7
Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205, Geneva, Switzerland. youssef.daali@hcuge.ch.
8
Geneva-Lausanne School of Pharmacy, University of Geneva, Geneva, Switzerland. youssef.daali@hcuge.ch.
9
Swiss Center for Applied Human Toxicology, Geneva, Switzerland. youssef.daali@hcuge.ch.
10
Faculty of Medicine, University of Geneva, Geneva, Switzerland. youssef.daali@hcuge.ch.

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.

PMID:
31131437
DOI:
10.1007/s40262-019-00783-z

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center