Zhao Xiao-Ping, Zhong Jiao, Liu Xiao-Quan, Wang Guang-Ji
Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
Acta Pharmacol Sin. 2007 Jan;28(1):118-24. doi: 10.1111/j.1745-7254.2007.00484.x.
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.
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 M(1) and M(2) in human liver microsomes.
Vinflunine was rapidly metabolized to 2 metabolites: M(1) and M(2) in human liver microsomes. M(1) and M(2) were tentatively presumed to be the N-oxide metabolite or hydroxylated metabolite and epoxide metabolite of vinflunine, respectively. Ketoconazole uncompetitively inhibited the formation of M(1), and competitively inhibited the formation of M(2), while alpha-naphthoflavone, sulfaphenazole, diethyl dithiocarbamate, tranylcypromine and quinidine had little or no inhibitory effect on the formation of M(1) and M(2).
Vinflunine is rapidly metabolized in human liver microsomes, and CYP3A4 is the major human CYP450 involved in the metabolism of vinflunine.
研究长春氟宁的代谢情况以及选择性细胞色素P-450（CYP450）抑制剂对长春氟宁在人肝微粒体中代谢的影响。
使用个体选择性CYP450抑制剂来研究它们对长春氟宁代谢的影响以及参与代谢物M(1)和M(2)形成的主要CYP450同工酶。
长春氟宁在人肝微粒体中迅速代谢为2种代谢物：M(1)和M(2)。M(1)和M(2)分别初步推测为长春氟宁的N-氧化物代谢物或羟基化代谢物以及环氧化物代谢物。酮康唑非竞争性抑制M(1)的形成，竞争性抑制M(2)的形成，而α-萘黄酮、磺胺苯唑、二乙基二硫代氨基甲酸盐、反苯环丙胺和奎尼丁对M(1)和M(2)的形成几乎没有抑制作用。
长春氟宁在人肝微粒体中迅速代谢，CYP3A4是参与长春氟宁代谢的主要人CYP450。
