Endobiotics for Phenotyping of Human Cytochrome P450 Enzymes
Status:
Recruiting
Trial end date:
2019-12-31
Target enrollment:
Participant gender:
Summary
CYP2D6 metabolizes ~25% of all marketed drugs. There is an important variability in the
activity of this enzyme among individuals. The cause of this variability might be
environmental, genetic, ethnical or even related to a disease. The administration of a CYP2D6
probe drug (e.g. dextromethorphan) is a good way to characterize CYP2D6 phenotype.
Nonetheless, it is relatively invasive and the vulnerable population (e.g. pregnant women)
cannot be phenotyped in this manner. Therefore, finding an endogenous substance which is
metabolized by CYP2D6 could replace usual phenotyping procedure using a probe drug. This
study evaluates the impact of a CYP2D6 inhibitor and of genetic polymorphism on the
metabolome of healthy volunteers in order to identify new CYP2D6 biomarkers. To this end,
untargeted metabolomics analysis using LC-HRMS will be performed on plasma and urine samples
This single-centre open-label clinical trial will include 40 healthy subjects (men and women)
between 18 and 65 years. Eligible participants will be assigned to a study group according to
their CYP2D6 genotypes: poor metabolizers (PMs) and extensive/ultrarapid metabolizers
(EMs-UMs). Two sessions will take place for each subjects.
Session 1: CYP2D6 phenotyping (dextromethorphan 5 mg, single dose) Session 2: idem session 1
with prior uptake of a CYP2D6 inhibitor (paroxetine 10 or 20 mg, one dose a day for 7 days).
In both sessions, urine will be collected up to 24 hours and capillary/venous blood will be
sampled before phenotyping for metabolomics analyses. Urine will also be collected for 4
hours after dextromethorphan intake in order to phenotype the CYP2D6 enzyme.