Pharmacogenetics

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Preventing the risk of adverse drug reaction and adapting treatment doses

CYP2D6 (Cytochrome P450, Family 2, Subfamily D, Polypeptide 6) is one of 57 cytochrome P450s, a class of metabolic enzymes found primarily in human liver cells.

Despite its low hepatic abundance (1–5 % of the CYP liver content), CYP2D6 accounts at least in part for the metabolism of up to 25 % of commonly prescribed drugs such as analgesics, antiarrhythmics, antidepressants, antipsychotics and others

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Description

The highly polymorphic nature of the CYP2D6 gene is a great source of variability in CYP2D6 drug substrates responses. The current phenotypic classification of CYP2D6 includes poor, intermediate, extensive or ultra-rapid metabolizers of CYP2D6 drug substrates.

  • Poor metabolizers have a low or no enzyme activity and are predicted by the presence of 2 non-functional alleles (activity score 0).
  • Intermediate metabolizers have reduced enzymatic activity and are predicted by the presence of two reduced activity alleles, or one reduced function allele et one non-functional allele, or one functional allele and one non-functional allele (activity score 0.5-1). Based on the specific context, the phenotype may overlap with a poor metabolizer or an extensive metabolizer.
  • Extensive metabolizers have normal enzymatic activity and are predicted by the presence of 2 functional alleles, or one functional allele and one reduced function allele (activity score 1-2).
  • Ultra-rapid metabolizers have increased enzymatic activity, and are predicted by the presence of more than 2 functional alleles (activity score >2).

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