CYP3A4基础与临床研究进展

细胞色素P4503A4(CYP3A4)是存在人类肝脏及肠道中的一种主要的细胞色素CYP450酶,约占成人肝脏CYP450酶总量的25%左右。临床中约有50%的药物是通过其代谢,并且其基因位点突变也与其多种疾病相关,知晓CYP3A4的表达水平和不同功能的遗传学基础,无论是对疾病的发病基础、临床药物的应用,会带来前所未有的启发,在药物应用过程中,通过对基因组学的认识,从而可以在基因层面了解个体代谢差异产生的原因,调整药物用量,提高疗效,最终使药物副作用降到最低限。目前对CYP3A4的研究渐趋于成熟,已逐渐阐明了其药物间相互作用的机制,它能够被多种药物竞争性抑制或者诱导,并受到某些蛋白受体的调控影响,可改变药物的药代动力学,增强或降低药效,造成个体用药差异,这也是造成药物间相互作用的重要原因。然而CYP3A4基因多态性与基因导向治疗关系,还有待进一步深入研究。该文对CYP3A4基因多态性、分布以及与临床疾病及用药的研究现状作一综述。

CYP3A4 Basic and Clinical Research Progress

Cytochrome P4503A4 （CYP3A4） is a kind of main enzymes exist in human liver and intestinal, accounted for about 25% of the total adult liver CYP450 enzyme. About 50% of the Clinical medicine is through its metabolism, and its gene locus mutation associated with a variety of diseases, the study of CYP3A4 is grinding to a mature, has been gradually clarified the mechanism of interaction between the drug, it can be a variety of drugs competitive inhibition or induction, and affected by certain protein receptors in the regulation and control, can change the pharmacokinetics of drugs, enhance or reduce the effect, caused by individual differences, this also is the important cause of drug interactions. CYP3A4 gene polymorphism and genetic relationship oriented treatment, however, further studies are needed. This paper for CYP3A4 gene polymorphism, distribution and clinical disease and drug review summarizes the current research status.