Impact of CYP2D6 Functional Allelic Variations on Phenoconversion and Drug-Drug Interactions.

Détails

ID Serval
serval:BIB_FA4006F6CCD1
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Impact of CYP2D6 Functional Allelic Variations on Phenoconversion and Drug-Drug Interactions.
Périodique
Clinical pharmacology and therapeutics
Auteur(s)
Storelli F., Matthey A., Lenglet S., Thomas A., Desmeules J., Daali Y.
ISSN
1532-6535 (Electronic)
ISSN-L
0009-9236
Statut éditorial
Publié
Date de publication
07/2018
Peer-reviewed
Oui
Volume
104
Numéro
1
Pages
148-157
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
We investigated whether CYP2D6 extensive metabolizers carrying a nonfunctional allele are at higher risk of phenoconversion to poor metabolizers in the presence of CYP2D6 inhibitors. Seventeen homozygous carriers of two fully-functional alleles and 17 heterozygous carriers of one fully-functional and one nonfunctional allele participated in this trial. Dextromethorphan 5 mg and tramadol 10 mg were given at each of the three study sessions. CYP2D6 was inhibited by duloxetine 60 mg (session 2) and paroxetine 20 mg (session 3). A higher rate of phenoconversion to intermediate metabolizers with duloxetine (71% vs. 25%, P = 0.009) and to poor metabolizers with paroxetine (94% vs. 56%, P = 0.011) was observed in heterozygous than homozygous extensive metabolizers. The magnitude of drug-drug interaction between dextromethorphan and paroxetine was higher in homozygous than in heterozygous subjects (14.6 vs. 8.5, P < 0.028). Our study suggests that genetic extensive metabolizers may not represent a homogenous population and that available genetic data should be considered when addressing drug-drug interactions in clinical practice.
Mots-clé
CYP2D6, activity score, drug-drug interactions, genotype-phenotype translation, heterozygous, pharmacogenetics, phenoconversion
Pubmed
Web of science
Création de la notice
25/09/2017 10:56
Dernière modification de la notice
20/08/2019 16:25
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