In vitro metabolism of chloroquine: identification of CYP2C8, CYP3A4, and CYP2D6 as the main isoforms catalyzing N-desethylchloroquine formation.

@article{Projean2003InVM,
  title={In vitro metabolism of chloroquine: identification of CYP2C8, CYP3A4, and CYP2D6 as the main isoforms catalyzing N-desethylchloroquine formation.},
  author={D. Projean and B. Baune and R. Farinotti and Jean-Pierre Flinois and P. Beaune and A. Taburet and J. Ducharme},
  journal={Drug metabolism and disposition: the biological fate of chemicals},
  year={2003},
  volume={31 6},
  pages={
          748-54
        }
}
  • D. Projean, B. Baune, +4 authors J. Ducharme
  • Published 2003
  • Biology, Medicine
  • Drug metabolism and disposition: the biological fate of chemicals
  • In humans, the antimalarial drug chloroquine (CQ) is metabolized into one major metabolite, N-desethylchloroquine (DCQ). Using human liver microsomes (HLM) and recombinant human cytochrome P450 (P450), we performed studies to identify the P450 isoform(s) involved in the N-desethylation of CQ. In HLM incubated with CQ, only DCQ could be detected. Apparent Km and Vmax values (mean +/- S.D.) for metabolite formation were 444 +/- 121 microM and 617 +/- 128 pmol/min/mg protein, respectively. In… CONTINUE READING
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    References

    SHOWING 1-10 OF 46 REFERENCES
    Amodiaquine clearance and its metabolism to N-desethylamodiaquine is mediated by CYP2C8: a new high affinity and turnover enzyme-specific probe substrate.
    • 259
    • PDF
    Metabolism of the antidepressant mirtazapine in vitro: contribution of cytochromes P-450 1A2, 2D6, and 3A4.
    • 121
    • Highly Influential
    • PDF
    Distinction of CYP1A1 and CYP1A2 activity by selective inhibition using fluvoxamine and isosafrole.
    • 79
    Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of rosiglitazone.
    • 220
    The xenobiotic inhibitor profile of cytochrome P4502C8.
    • 87
    Selective biotransformation of taxol to 6 alpha-hydroxytaxol by human cytochrome P450 2C8.
    • 409
    Effect of selected antimalarial drugs and inhibitors of cytochrome P-450 3A4 on halofantrine metabolism by human liver microsomes.
    • 34
    • PDF
    Differential selectivity of cytochrome P450 inhibitors against probe substrates in human and rat liver microsomes.
    • 311
    • Highly Influential