摘要
CYP3A酶主要分布于人体肝脏和小肠,广泛参与各种药物代谢。该酶在介导药物代谢的同时也会受底物影响,其活性被诱导或抑制,从而影响其他经由CYP3A酶代谢的药物体内过程。目前可以通过体外探针药物和内源性生物标志物评价CYP3A酶活性,前者需要口服探针药物,后者只需检测内源性标志物如4β-羟基胆固醇和6β-羟基氢化可的松。文献报道,研究CYP3A酶活性除了有助于阐明不同个体的药物代谢差异,还可以提示药物相互作用情况下合用药物的剂量调整,预测药物疗效和毒性反应,为个体化用药提供理论指导,评估新药潜在的药物相互作用,降低新药上市风险。笔者对上述2种常用的内源性标志物的相关研究和临床应用进行综述。
Human cytochrome P450 （CYP） 3A ,which is widely involved in the various drug metabolism ,is most abun-dant in liver and intestine .The activity of CYP3A enzyme may be induced or inhibited in the process of drug metabolisms ,and affect the metabolism of other CYP3A substrates and modulators vice versa .At present ,in vitro probe drugs and in vivo bio-markers are both available to evaluate the activity of CYP 3A enzyme .The former requires oral probe drugs ,the latter does not need for those drugs and just allows laboratory technicians to detect endogenous substrates ,such as 4β-hydroxycholesterol and 6β-hydroxycortisol .As reported ,studies on CYP3A help to explain the inter-individually variability in drug metabolism ,to in-dicate dose adjustments in combination regimens when drug interactions exist ,to predict drug efficacy and toxicity reaction for providing theoretical guidance for individualized medication ,and to reduce market risk of new drugs for the potential drug inter-actions .We summarized these two kinds of endogenous biomarkers and their clinical application in this review .
出处
《药学实践杂志》
CAS
2016年第5期385-388,402,共5页
Journal of Pharmaceutical Practice
基金
国家自然科学基金面上项目(81573793)
