title: Effect of CYP2D6, CYP2C9 and ABCB1 genotypes on fluoxetine plasma concentrations and clinical improvement in children and adolescent patients.
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.
authors.affiliation: 1] Department of Anatomic Pathology, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain [2] Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Gassó
authors.affiliation: Department of Anatomic Pathology, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Rodríguez
authors.affiliation: 1] Department of Anatomic Pathology, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain [2] Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain [3] Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Mas
authors.affiliation: Department of Anatomic Pathology, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Pagerols
authors.affiliation: Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clinic de Barcelona, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Blázquez
authors.affiliation: Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clinic de Barcelona, Barcelona, Spain.
authors.forename: M T
authors.initials: MT
authors.lastname: Plana
authors.affiliation: Pharmacology and Toxicology Department, CDB, Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Torra
authors.affiliation: 1] Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain [2] Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain [3] Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clinic de Barcelona, Barcelona, Spain [4] Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Lázaro
authors.affiliation: 1] Department of Anatomic Pathology, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain [2] Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain [3] Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Lafuente
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D002648:Child; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics* / Q000378:metabolism; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005473:Fluoxetine / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005838:Genotype; D006801:Humans; D008297:Male
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D005473:Fluoxetine; D065729:Cytochrome P-450 CYP2C9; D019389:Cytochrome P-450 CYP2D6