次黄嘌呤单核苷酸脱氢酶的活性测定及临床应用  

The determination and clinical application of inosine 5'-monophosphate dehydrogenase activity

作　　者：刘飞燕[1] 邱晓燕[1] 焦正[1] 

机构地区：[1]复旦大学附属华山医院药剂科,上海200040

出　　处：《药学学报》2016年第11期1666-1673,共8页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81573505;81302854);上海市科学技术委员会医学引导类(西医)资助项目(15411968000)

摘　　要：次黄嘌呤单核苷酸脱氢酶(IMPDH)是一种鸟嘌呤从头合成途径的限速酶,在细胞增殖过程中发挥着重要作用。目前临床常用的作用于IMPDH的药物为IMPDH抑制剂,主要应用于抗免疫排斥、抗肿瘤、抗病毒或抗寄生虫等领域。IMPDH抑制剂的血药浓度与临床疗效之间存在一定关联性。但由于该关联的个体间变异通常较大,故测定IMPDH酶活性可作为一项监测其药物疗效的特异性生物标志物,与药动学监测相结合,可提高IMPDH抑制剂临床应用的安全性和有效性。本文旨在综述国内外近年来有关IMPDH酶活性的测定方法与临床应用现状,为临床IMPDH抑制剂药效学监测的开展和应用提供方法与依据。Inosine 5＇-monophosphate dehydrogenase （IMPDH） is a rate-limiting enzyme in de novo biosynthesis of guanine and plays an important role in cell proliferation. In clinic, IMPDH inhibitors are mainly used in fields of anticancer, antiviral, anti-parasitic, and immunosuppressive chemotherapy. However, since there are usually great inter- and intra-individual variability between drug concentration and clinical effect of IMPDH inhibitors, the enzyme activity of IMPDH may be applied as a specific biomarker and combined with the pharmacokinetics （PK） monitoring to improve efficacy and safety of IMPDH inhibitors. This review aims to discuss the assay of IMPDH activity measurement and its clinical application in recent years and provide valuable insights and theoretical basis for the development of IMPDH inhibitors＇ pharmacodynamics monitoring.

关 键 词：次黄嘌呤单核苷酸脱氢酶 次黄嘌呤单核苷酸脱氢酶抑制剂 酶活性测定 生物标志物 

分 类 号：R963[医药卫生—微生物与生化药学]