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
Author(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
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 18:18
Last modification date
20/08/2019 16:10
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