Population pharmacokinetic study of memantine: effects of clinical and genetic factors.
Details
Serval ID
serval:BIB_6598521C6000
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Population pharmacokinetic study of memantine: effects of clinical and genetic factors.
Journal
Clinical pharmacokinetics
ISSN
1179-1926 (Electronic)
ISSN-L
0312-5963
Publication state
Published
Issued date
03/2013
Peer-reviewed
Oui
Volume
52
Number
3
Pages
211-223
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
Memantine, a frequently prescribed anti-dementia drug, is mainly eliminated unchanged by the kidneys, partly via tubular secretion. Considerable inter-individual variability in plasma concentrations has been reported. We aimed to investigate clinical and genetic factors influencing memantine disposition.
A population pharmacokinetic study was performed including data from 108 patients recruited in a naturalistic setting. Patients were genotyped for common polymorphisms in renal cation transporters (SLC22A1/2/5, SLC47A1, ABCB1) and nuclear receptors (NR1I2, NR1I3, RXR, PPAR) involved in transporter expression.
The average clearance was 5.2 L/h with a 27 % inter-individual variability (percentage coefficient of variation). Glomerular filtration rate (p = 0.007) and sex (p = 0.001) markedly influenced memantine clearance. NR1I2 rs1523130 was identified as the unique significant genetic covariate for memantine clearance (p = 0.006), with carriers of the NR1I2 rs1523130 CT/TT genotypes presenting a 16 % slower memantine elimination than carriers of the CC genotype.
The better understanding of inter-individual variability of memantine disposition might be beneficial in the context of individual dose optimization.
A population pharmacokinetic study was performed including data from 108 patients recruited in a naturalistic setting. Patients were genotyped for common polymorphisms in renal cation transporters (SLC22A1/2/5, SLC47A1, ABCB1) and nuclear receptors (NR1I2, NR1I3, RXR, PPAR) involved in transporter expression.
The average clearance was 5.2 L/h with a 27 % inter-individual variability (percentage coefficient of variation). Glomerular filtration rate (p = 0.007) and sex (p = 0.001) markedly influenced memantine clearance. NR1I2 rs1523130 was identified as the unique significant genetic covariate for memantine clearance (p = 0.006), with carriers of the NR1I2 rs1523130 CT/TT genotypes presenting a 16 % slower memantine elimination than carriers of the CC genotype.
The better understanding of inter-individual variability of memantine disposition might be beneficial in the context of individual dose optimization.
Keywords
Aged, Aged, 80 and over, Carrier Proteins/genetics, Constitutive Androstane Receptor, Dementia/drug therapy, Dementia/metabolism, Excitatory Amino Acid Antagonists/blood, Excitatory Amino Acid Antagonists/pharmacokinetics, Female, Genotype, Humans, Male, Memantine/blood, Memantine/pharmacokinetics, Membrane Transport Proteins/genetics, Middle Aged, Models, Biological, Polymorphism, Genetic, Receptors, Cytoplasmic and Nuclear/genetics
Pubmed
Web of science
Create date
25/02/2013 11:50
Last modification date
25/02/2023 6:46
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