Bargetzi M J, Aoyama T, Gonzalez F J, Meyer U A
Department of Pharmacology, Biocenter of the University, Basel, Switzerland.
Clin Pharmacol Ther. 1989 Nov;46(5):521-7. doi: 10.1038/clpt.1989.180.
The metabolism of lidocaine to its major metabolite monoethylglycinexylidide (MEGX) was studied in human liver microsomes of 13 kidney transplant donors and of one patient with liver cirrhosis. Interindividual variation in metabolite formation was considerable. Biphasic kinetics indicated the involvement of at least two distinct enzymatic activities. With use of a series of antisera that recognize different human cytochrome P450 isozymes, we were able to identify an enzyme of the P450III gene family as one of two enzymes. By expressing human P450IIIA4 complementary deoxyribonucleic acid (cDNA) in HepG2 cells, we directly demonstrated lidocaine-deethylase activity for this P450 isozyme. These data suggest that P450IIIA4 is at least in part responsible for microsomal MEGX formation.
在13名肾移植供体和1名肝硬化患者的人肝微粒体中研究了利多卡因向其主要代谢产物单乙基甘氨酰二甲苯胺（MEGX）的代谢情况。代谢产物形成的个体间差异相当大。双相动力学表明至少涉及两种不同的酶活性。通过使用一系列识别不同人类细胞色素P450同工酶的抗血清，我们能够确定P450III基因家族的一种酶是两种酶之一。通过在HepG2细胞中表达人P450IIIA4互补脱氧核糖核酸（cDNA），我们直接证明了该P450同工酶的利多卡因脱乙基酶活性。这些数据表明P450IIIA4至少部分负责微粒体MEGX的形成。
