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

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  • معلومة اضافية
    • المصدر:
      Publisher: Nature Pub. Group Country of Publication: United States NLM ID: 101083949 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1473-1150 (Electronic) Linking ISSN: 1470269X NLM ISO Abbreviation: Pharmacogenomics J Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: Avenet, NJ : Nature Pub. Group, c2001-
    • الموضوع:
      Cytochrome P-450 CYP2C9/*genetics ; Cytochrome P-450 CYP2D6/*genetics ; Fluoxetine/*blood ; Fluoxetine/*therapeutic use; ATP Binding Cassette Transporter, Subfamily B/genetics ; ATP Binding Cassette Transporter, Subfamily B/metabolism ; Adolescent ; Child ; Cytochrome P-450 CYP2C9/metabolism ; Cytochrome P-450 CYP2D6/metabolism ; Female ; Fluoxetine/pharmacokinetics ; Genotype ; Humans ; Male
    • نبذة مختصرة :
      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.
    • الرقم المعرف:
      0 (ABCB1 protein, human)
      0 (ATP Binding Cassette Transporter, Subfamily B)
      01K63SUP8D (Fluoxetine)
      EC 1.14.13.- (Cytochrome P-450 CYP2C9)
      EC 1.14.14.1 (Cytochrome P-450 CYP2D6)
    • الموضوع:
      Date Created: 20140326 Date Completed: 20151012 Latest Revision: 20220331
    • الموضوع:
      20240829
    • الرقم المعرف:
      10.1038/tpj.2014.12
    • الرقم المعرف:
      24663076