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Aim:To study the metabolism of vinflunine and the effects of selective cyto-chrome P-450(CYP450)inhibitors on the metabolism of vinflunine in human livermicrosomes.Methods:Individual selective CYP450 inhibitors were used to inves-tigate their effects on the metabolism of vinflunine and the principal CYP450 isoforminvolved in the formation of metabolites M_1 and M_2 in human liver microsomes.Results:Vinflunine was rapidly metabolized to 2 metabolites:M_1 and M_2 in humanliver microsomes.M_1 and M_2 were tentatively presumed to be the N-oxide metabo-lite or hydroxylated metabolite and epoxide metabolite of vinflunine,respectively.Ketoconazole uncompetitively inhibited the formation of M_1,and competitivelyinhibited the formation of M_2,while α-naphthoflavone,sulfaphenazole,diethyldithiocarbamate,tranylcypromine and quinidine bad little or no inhibitory effecton the formation of M_1 and M_2.Conclusion:Vinflunine is rapidly metabolized inhuman liver microsomes,and CYP3A4 is the major human CYP450 involved in themetabolism of vinflunine.
Aim: To study the metabolism of vinflunine and the effects of selective cyto-chrome P-450 (CYP450) inhibitors on the metabolism of vinflunine in human liver microorganisms. Methods: Individual selective CYP450 inhibitors were used to investe tigate their effects on the metabolism of vinflunine and the principal CYP450 isoforminvolved in the formation of metabolites M_1 and M_2 in human liver microsomes.Results: Vinflunine was rapidly metabolized to 2 metabolites: M_1 and M_2 in humanliver microsomes. M_1 and M_2 were tentatively presumed to be the N-oxide metabo- lite or hydroxylated metabolite and epoxide metabolite of vinflunine, respectively. respectively. Ketoconazole uncompetitively inhibited the formation of M_1, and competitively inhibited by the formation of M_2, while α-naphthoflavone, sulfaphenazole, diethyldithiocarbamate, tranylcypromine and quinidine bad little or no inhibitory effect of the formation of M_1 and M_2.Conclusion: Vinflunine is rapidly metabolized inhuman liver microsomes, and CYP3A4 is the major huma n CYP450 involved in themetabolism of vinflunine.