嘌呤类药物代谢酶和代谢物与药物反应关联及影响因素研究进展  

Advance in the association study between metabolizing enzymes,metabolites of thiopurines and drug reactions as well as their influencing factors

作　　者：师少军[1,2] 张玉[1] SHI Shao-jun;ZHANG Yu(Department of Pharmacy,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Hubei Wuhan 430022,China;Department of Pharmacy,union Jiangnan Hospital,Huazhong University of science and Technology,Hubei Wuhan 434200,China)

机构地区：[1]华中科技大学同济医学院附属协和医院药学部,湖北武汉430022 [2]华中科技大学协和江南医院药剂科,湖北武汉434200

出　　处：《中国医院药学杂志》2020年第24期2605-2610,共6页Chinese Journal of Hospital Pharmacy

基　　金：国家自然科学基金面上项目(编号:81874326);国家重点研发计划资助项目(编号:2017YFC0909900)。

摘　　要：临床上嘌呤类药物作为免疫抑制剂广泛应用于治疗实体器官移植、自身免疫性疾病和炎症性肠病、儿童急性淋巴细胞性白血病等疾病,但该类药物体内处置个体间差异大,治疗窗窄,且所致不良反应(如肾毒性和肝毒性)发生率较高。本文综述近年来嘌呤类药物代谢酶(TPMT、NDPK、ITPA、GST、XO/XDH、HGPRT、IMPDH和NUDT15)和代谢物(6-MMPR、6-TGNs、6-TGTP)对该类药物临床疗效和不良反应的影响,以及患者服药剂量和疗程、性别、年龄、体质量、遗传等多因素对代谢酶和代谢物影响的研究进展。研究表明该类药物临床疗效和不良反应与其体内代谢酶活性和代谢物浓度密切相关,但结论并不完全一致,因此有待大规模临床研究进一步验证以上关联性及影响因素。Purines are widely used as immunosuppressive agents in the treatment of solid organ transplantation,autoimmune diseases,inflammatory bowel disease,childhood acute lymphoblastic leukemia and other diseases.However,the in vivo disposition of these drugs varies greatly among individuals,the therapeutic window is narrow,and the incidence of adverse reactions(such as nephrotoxicity and hepatotoxicity) is high.This article reviews the effects of purine metabolizing enzymes(TPMT,NDPK,ITPA,GST,XO/XDH,HGPRT,IMPDH,and NUDT15) and metabolites(6-MMPR,6-TGNs,and 6-TGTP) on the clinical efficacy and adverse reactions of this class of drugs in recent years.The research progress on the effects of multiple factors such as dosage and course of treatment,gender,age,weight,and genetics on metabolic enzymes and metabolites was also analyzed.Studies have shown that the clinical efficacy and adverse reactions of these drugs are closely related to their metabolic enzyme activities and metabolite concentrations in vivo,but the conclusions are not completely consistent,so large-scale clinical studies are needed to further verify the above correlation and influencing factors.

关 键 词：嘌呤类药物 代谢酶 代谢物 临床疗效 不良反应 关联研究 影响因素 

分 类 号：R969[医药卫生—药理学]