Identification of Cytochrome P450 Isoforms Involved in the Metabolism of Paroxetine and Estimation of Their Importance for Human Paroxetine Metabolism Using a Population-Based Simulator

@article{Jornil2010IdentificationOC,
  title={Identification of Cytochrome P450 Isoforms Involved in the Metabolism of Paroxetine and Estimation of Their Importance for Human Paroxetine Metabolism Using a Population-Based Simulator},
  author={Jakob R Jornil and Klaus Gjervig Jensen and Frank Larsen and Kristian Linnet},
  journal={Drug Metabolism and Disposition},
  year={2010},
  volume={38},
  pages={376 - 385}
}
We identify here for the first time the low-affinity cytochrome P450 (P450) isoforms that metabolize paroxetine, using cDNA-expressed human P450s measuring substrate depletion and paroxetine-catechol (product) formation by liquid chromatography-tandem mass spectrometry. CYP1A2, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 were identified as paroxetine-catechol-forming P450 isoforms, and CYP2C19 and CYP2D6 were identified as metabolizing P450 isoforms by substrate depletion. Michaelis-Menten constants Km… 
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64 Citations
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The findings of this study suggest that the CYP2D6*10 polymorphism may be associated with the smaller values of both the Km and Vmax in Japanese patients with major depressive disorders, and these results need to be confirmed in further investigations with a larger number of patients.
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