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Effect of CYP2D6, CYP2C9 and ABCB1 genotypes on fluoxetine plasma concentrations and clinical improvement in children and adolescent patients

The Pharmacogenomics Journal volume 14, pages 457–462 (2014)Cite this article

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Abstract

There is little known about pharmacogenetic of fluoxetine in children and adolescents. In this study, we evaluate, for the first time, the influence of CYP2D6, CYP2C9 and ABCB1 genotypes on the steady-state plasma concentrations of fluoxetine and its active metabolite (S)-norfluoxetine, and on the clinical improvement in children and adolescent patients receiving fluoxetine treatment. The assessment was performed in 83 patients after 8 and 12 weeks of treatment. Fluoxetine/(S)-norfluoxetine ratio was negatively correlated with the number of active CYP2D6 alleles (r: −0.450; P<0.001). Regarding the G2677T ABCB1 polymorphism, T allele carriers showed significantly higher improvements on the majority of scales including the Clinical Global Impression-Improvement scale (P<0.001). Our results confirm the influence of CYP2D6 genetic variants in fluoxetine pharmacokinetics and provide evidence for the potential effect of the ABCB1 genotype on the clinical improvement in children and adolescent patients treated with fluoxetine.

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Acknowledgements

This work was supported by the Spanish Ministry of Health, Instituto Carlos III, Fondo de Investigación Sanitaria (FIS) (PI041239 and ‘Sara Borrell’ contract CD09/00296 to PG); the Catalan Innovation, Universities and Enterprise Authority (grants DIUE 2009SGR1295, 2009SGR1501, 2009SGR1119); Alicia Koplowitz Foundation; and FEDER-Unión Europea. We thank Rosa Abellana for help in the statistical analysis, and the Language Advisory Service at the University of Barcelona, Spain, for manuscript revision.

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Authors and Affiliations

  1. Department of Anatomic Pathology, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain

    P Gassó, N Rodríguez, S Mas, M Pagerols & A Lafuente

  2. Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    P Gassó, S Mas, L Lázaro & A Lafuente

  3. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain

    S Mas, L Lázaro & A Lafuente

  4. Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clinic de Barcelona, Barcelona, Spain

    A Blázquez, M T Plana & L Lázaro

  5. Pharmacology and Toxicology Department, CDB, Hospital Clínic de Barcelona, Barcelona, Spain

    M Torra

  6. Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain

    L Lázaro

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  1. P Gassó
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Correspondence to A Lafuente.

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Gassó, P., Rodríguez, N., Mas, S. et al. Effect of CYP2D6, CYP2C9 and ABCB1 genotypes on fluoxetine plasma concentrations and clinical improvement in children and adolescent patients. Pharmacogenomics J 14, 457–462 (2014). https://doi.org/10.1038/tpj.2014.12

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  • DOI: https://doi.org/10.1038/tpj.2014.12

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