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

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Noetzli M, Guidi M, Ebbing K, Eyer S, Wilhelm L, Michon A, Thomazic V, Alnawaqil AM, Maurer S, Zumbach S, Giannakopoulos P, von Gunten A, Csajka C, Eap CB

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

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

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23371894 [ View in PubMed
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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.

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