Abstract
Aim:
To study the metabolism of vinflunine and the effects of selective cytochrome P-450 (CYP450) inhibitors on the metabolism of vinflunine in human liver microsomes.
Methods:
Individual selective CYP450 inhibitors were used to investigate their effects on the metabolism of vinflunine and the principal CYP450 isoform involved in the formation of metabolites M1 and M2 in human liver microsomes.
Results:
Vinflunine was rapidly metabolized to 2 metabolites: M1 and M2 in human liver microsomes. M1 and M2 were tentatively presumed to be the N-oxide metabolite or hydroxylated metabolite and epoxide metabolite of vinflunine, respectively. Ketoconazole uncompetitively inhibited the formation of M1, and competitively inhibited the formation of M2, while α-naphthoflavone, sulfaphenazole, diethyl dithiocarbamate, tranylcypromine and quinidine had little or no inhibitory effect on the formation of M1 and M2.
Conclusion:
Vinflunine is rapidly metabolized in human liver microsomes, and CYP3 A4 is the major human CYP450 involved in the metabolism of vinflunine.
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Project supported by the National High Technology 863 project (No 2003AA2Z347A) and Jiangsu Key Laboratory of Drug Metabolism and Pharmacokinetics (No BM2001201).
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Zhao, Xp., Zhong, J., Liu, Xq. et al. CYP3A4 mediated in vitro metabolism of vinflunine in human liver microsomes. Acta Pharmacol Sin 28, 118–124 (2007). https://doi.org/10.1111/j.1745-7254.2007.00484.x
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DOI: https://doi.org/10.1111/j.1745-7254.2007.00484.x
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