Relationship of CYP2D6, CYP3A, POR, and ABCB1 Genotypes With Galantamine Plasma Concentrations.
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State: Public
Version: author
Serval ID
serval:BIB_A5DFF6BBD3DF
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Relationship of CYP2D6, CYP3A, POR, and ABCB1 Genotypes With Galantamine Plasma Concentrations.
Journal
Therapeutic Drug Monitoring
ISSN
1536-3694 (Electronic)
ISSN-L
0163-4356
Publication state
Published
Issued date
2013
Peer-reviewed
Oui
Volume
35
Number
2
Pages
270-275
Language
english
Notes
Publication types: JOURNAL ARTICLEPublication Status: ppublish
Abstract
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
Create date
12/04/2013 17:18
Last modification date
20/08/2019 15:10