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Clin Pharmacokinet. 2013 Mar;52(3):211-23. doi: 10.1007/s40262-013-0032-2.

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

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1
Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Hospital of Cery, University Hospital Lausanne, 1008 Prilly-Lausanne, Switzerland.

Abstract

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.

PMID:
23371894
DOI:
10.1007/s40262-013-0032-2
[Indexed for MEDLINE]
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