Polymorphisms in the CYP 2D6 Gene: Association with Plasma Concentrations of Fluoxetine and Paroxetine

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Abstract
Most antidepressants are metabolized by cytochrome P450 (CYP) 2D6, and it is well known that there may be significant interindividual variation in the capacity to metabolize xenobiotics. About 7 to 10% of whites are poor metabolisers (PM), and, on the contrary, about 5% are ultrarapid metabolizers (UM), inducing very different rates in the transformation of antidepressants extensively metabolized by CYP 2D6. CYP 2D6 polymorphism can be a potential risk factor for the development of side effects or a reason for the poor efficacy of the treatment. Various probe drugs may be used for phenotyping CYP 2D6, but genotyping is now available using leukocyte DNA and is independent of concomitant drug use. In this study, we used PCR-based methods for the identification of CYP 2D6 genotypes in 49 patients receiving standard doses of fluoxetine or paroxetine and found that plasma concentration of the antidepressant drugs was significantly correlated with genetic status. In one patient who displayed CYP 2D6 gene duplication (UM), paroxetine plasma concentration was extremely low. In PM fluoxetine-treated patients, drug plasma concentration was significantly higher than that seen in extensive metabolizers.

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