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={J. Jornil and K. G. Jensen and Frank Larsen and K. Linnet},
  journal={Drug Metabolism and Disposition},
  year={2010},
  volume={38},
  pages={376 - 385}
}
  • J. Jornil, K. G. Jensen, +1 author K. Linnet
  • Published 2010
  • Chemistry, Medicine
  • Drug Metabolism and Disposition
  • 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… CONTINUE READING
    60 Citations

    Tables and Topics from this paper

    Predicted contributions of cytochrome P450s to drug metabolism in human liver microsomes using relative activity factor were dependent on probes
    • S. Wang, Xiange Tang, +4 authors L. Liu
    • Chemistry, Medicine
    • Xenobiotica; the fate of foreign compounds in biological systems
    • 2019
    • 2
    Evaluation of Hepatic Disposition of Paroxetine Using Sandwich-Cultured Rat and Human Hepatocytes
    • 12
    • PDF
    Effect of Cytochrome P450 polymorphism on the action and metabolism of selective serotonin reuptake inhibitors
    • 24

    References

    SHOWING 1-10 OF 33 REFERENCES
    The role of cytochrome P4502D6 in the metabolism of paroxetine by human liver microsomes.
    • 115
    • Highly Influential
    NADPH-dependent covalent binding of [3H]paroxetine to human liver microsomes and S-9 fractions: identification of an electrophilic quinone metabolite of paroxetine.
    • 53
    Roles of polymorphic enzymes CYP2D6 and CYP2C19 for in vitro metabolism of amitriptyline at therapeutic and toxic levels
    • 5
    Apparent mechanism-based inhibition of human CYP2D6 in vitro by paroxetine: comparison with fluoxetine and quinidine.
    • 224
    • Highly Influential
    • PDF
    Drugs as CYP3A Probes, Inducers, and Inhibitors
    • 162
    Metoprolol-paroxetine interaction in human liver microsomes: stereoselective aspects and prediction of the in vivo interaction.
    • 30
    Mechanism-Based Inactivation of Human Cytochrome P450 Enzymes and the Prediction of Drug-Drug Interactions
    • 351
    • Highly Influential
    • PDF