Population pharmacokinetic study of memantine: effects of clinical and genetic factors.

Détails

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Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_6598521C6000
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Population pharmacokinetic study of memantine: effects of clinical and genetic factors.
Périodique
Clinical Pharmacokinetics
Auteur(s)
Noetzli M., Guidi M., Ebbing K., Eyer S., Wilhelm L., Michon A., Thomazic V., Alnawaqil A.M., Maurer S., Zumbach S., Giannakopoulos P., von Gunten A., Csajka C., Eap C.B.
ISSN
0312-5963 (Print)
ISSN-L
0312-5963
Statut éditorial
Publié
Date de publication
2013
Peer-reviewed
Oui
Volume
52
Numéro
3
Pages
211-223
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: ppublish
Résumé
BACKGROUND AND OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: The better understanding of inter-individual variability of memantine disposition might be beneficial in the context of individual dose optimization.
Pubmed
Web of science
Création de la notice
25/02/2013 11:50
Dernière modification de la notice
20/08/2019 14:21
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