Impact of Genetic Polymorphism on Drug-Drug Interactions Involving CYP2D6
Status:
Completed
Trial end date:
2018-12-01
Target enrollment:
Participant gender:
Summary
CYP2D6 is characterized by a huge variability in the general population, mainly because of
genetic polymorphism and drug-drug interactions (DDIs). CYP2D6 genotype is known to have an
impact on the extent of DDIs. Indeed several studies have pointed out differential DDIs
extent according to CYP2D6 genotype. The terms phenoconversion and phenotype switch are both
used to describe the phenomenon by which a given subject changes his phenotype to another due
external influence such as DDIs. When given a sufficiently strong CYP2D6 inhibitor, the
phenotype of an individual with no mutant allele (extensive metabolizer, EM) of CYP2D6 can be
modified to a poor metabolizer (PM) phenotype. This vulnerability is also thought to be
dependent on CYP2D6 genotype. Various combinations of alleles predict an EM genotype, which
represents about 60 to 70% of the general population. The aim of the study is to determine
whether the presence of genetic mutation in CYP2D6 has an impact on DDIs involving the CYP2D6
enzyme. Our interest focuses on CYP2D6 EM carriers of two fully functional alleles and
carriers of one non-functional and one functional allele. In order to elucidate this
question, CYP2D6 activity will be measured on healthy volunteers by administration of single
low doses of dextromethorphan and tramadol in presence or not of duloxetine and paroxetine,
two known CYP2D6 inhibitors.