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Population Pharmacokinetic Study of Memantine: Effects of Clinical and Genetic Factors

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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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Acknowledgments

We thank N. Laverrière, Dr F. Sali, Dr G. Schopf, Dr V. Falciola, Dr C. Costa, Dr M. Benouioua, Dr M. Quiroz, Dr P. Roungas and Dr T. Bui for patient enrolment, A. Kottelat, M. Brocard, M. Delessert, N. Cochard, C. Brogli, V. Hodel and A.C. Aubert for sample analyses, K. Powell Golay for editorial assistance and E. Ponce for help with bibliography. We thank the Vital-IT (http://www.vital-it.ch) Center for High-Performance Computing of the Swiss Institute of Bioinformatics for providing the computational resources for the population analyses.

Conflict of interest

The authors declare no conflict of interest.

Funding

This study was supported by internal funds of the Unit of Pharmacogenetics and Clinical Psychopharmacology, Department of Psychiatry, University Hospital Lausanne and by a private donation (Irène Allenbach) in support of research on Alzheimer’s disease.

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Authors and Affiliations

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

    Muriel Noetzli, Sophie Maurer & Chin B. Eap

  2. Division of Clinical Pharmacology, Department of Laboratories, University Hospital Lausanne, Lausanne, Switzerland

    Monia Guidi & Chantal Csajka

  3. Service of Old Age Psychiatry, Department of Psychiatry, University Hospital Lausanne, Prilly-Lausanne, Switzerland

    Karsten Ebbing & Armin von Gunten

  4. Geriatric Medicine and Geriatric Rehabilitation, Department of Medicine, University Hospital Lausanne, Lausanne, Switzerland

    Stephan Eyer

  5. Fondation Nant, Consultation Aigle, Aigle, Switzerland

    Laurence Wilhelm

  6. Division of Geriatric Psychiatry Department of Psychiatry, University Hospital Geneva, Geneva, Switzerland

    Agnès Michon & Valérie Thomazic

  7. Fribourg Mental Health Network, Department of Psychiatry, Cantonal Hospital Fribourg, Marsens, Switzerland

    Abdel-Messieh Alnawaqil & Serge Zumbach

  8. Division of General Psychiatry, Department of Mental Health and Psychiatry, University Hospital Geneva, Geneva, Switzerland

    Panteleimon Giannakopoulos

  9. School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland

    Monia Guidi, Chantal Csajka & Chin B. Eap

Authors
  1. Muriel Noetzli
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  2. Monia Guidi
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  9. Sophie Maurer
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  13. Chantal Csajka
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  14. Chin B. Eap
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Corresponding author

Correspondence to Chin B. Eap.

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Noetzli, M., Guidi, M., Ebbing, K. et al. Population Pharmacokinetic Study of Memantine: Effects of Clinical and Genetic Factors. Clin Pharmacokinet 52, 211–223 (2013). https://doi.org/10.1007/s40262-013-0032-2

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