Relationship of CYP2D6, CYP3A, POR, and ABCB1 Genotypes With Galantamine Plasma Concentrations.

Détails

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Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_A5DFF6BBD3DF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Relationship of CYP2D6, CYP3A, POR, and ABCB1 Genotypes With Galantamine Plasma Concentrations.
Périodique
Therapeutic Drug Monitoring
Auteur(s)
Noetzli M., Guidi M., Ebbing K., Eyer S., Zumbach S., Giannakopoulos P., von Gunten A., Csajka C., Eap C.B.
ISSN
1536-3694 (Electronic)
ISSN-L
0163-4356
Statut éditorial
Publié
Date de publication
2013
Peer-reviewed
Oui
Volume
35
Numéro
2
Pages
270-275
Langue
anglais
Notes
Publication types: JOURNAL ARTICLEPublication Status: ppublish
Résumé
BACKGROUND:: The frequently prescribed antidementia drug galantamine is extensively metabolized by the enzymes cytochrome P450 (CYP) 2D6 and CYP3A and is a substrate of the P-glycoprotein. We aimed to study the relationship between genetic variants influencing the activity of these enzymes and transporters with galantamine steady state plasma concentrations. METHODS:: In this naturalistic cross-sectional study, 27 older patients treated with galantamine were included. The patients were genotyped for common polymorphisms in CYP2D6, CYP3A4/5, POR, and ABCB1, and galantamine steady state plasma concentrations were determined. RESULTS:: The CYP2D6 genotype seemed to be an important determinant of galantamine pharmacokinetics, with CYP2D6 poor metabolizers presenting 45% and 61% higher dose-adjusted galantamine plasma concentrations than heterozygous and homozygous CYP2D6 extensive metabolizers (median 2.9 versus 2.0 ng/mL·mg, P = 0.025, and 1.8 ng/mL·mg, P = 0.004), respectively. CONCLUSIONS:: The CYP2D6 genotype significantly influenced galantamine plasma concentrations. The influence of CYP2D6 polymorphisms on the treatment efficacy and tolerability should be further investigated.
Pubmed
Web of science
Création de la notice
12/04/2013 17:18
Dernière modification de la notice
20/08/2019 15:10
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