尿苷二磷酸葡醛酸转移酶介导的酪氨酸激酶抑制剂药物相互作用研究进展  

Advances in uridine diphosphate glucuronosyltransferase-mediated drug interactions with tyrosine kinase inhibitors

作　　者：何雪茹 付裕豪 荀雪姣 崔艳军 董占军[2] HE Xueru;FU Yuhao;XUN Xuejiao;CUI Yanjun;DONG Zhanjun(Graduate School of Hebei Medical University,Shijiazhuang 050011,Hebei,China;Department of Pharmacy,Hebei Provincial People's Hospital,Shijiazhuang 050057,Hebei,China)

机构地区：[1]河北医科大学研究生院,河北石家庄050011 [2]河北省人民医院药学部,河北石家庄市050057

出　　处：《中国临床药理学与治疗学》2022年第8期936-945,共10页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：河北省医学科学研究课题(20210037)。

摘　　要：近年来由代谢酶和转运体介导的酪氨酸激酶抑制剂(TKIs)的药物相互作用(DDI)已成为临床治疗的一个重要问题。除CYP450酶,尿苷二磷酸葡醛酸转移酶(UGTs)是参与TKIs代谢的另一类代谢酶,而且在体外多数TKI对UGTs呈抑制作用。TKIs与UGTs底物或抑制剂联合用药可能发生潜在的有临床意义的DDI。本文将重点研究UGTs介导的TKIs的药物-药物相互作用以及UGT1A基因型对TKIs的药物相互作用的影响,并探讨解决策略,以期为临床医师和药师对TKIs的安全合理应用提供参考。Drug-drug interactions(DDI)of tyrosine kinase inhibitors(TKIs)mediated by metabolic enzymes and transporters have become an important issue in clinical practice recently.In addition to CYP450 enzymes,uridine diphosphate glucuronidases(UGTs)are another class of metabolic enzymes involved in the metabolism of TKIs,and most TKIs can inhibit the UGTs in vitro.Potential clinically meaningful DDIs may occur with the coadministration of TKIs and substrates or inhibitors of UGTs.This paper will mainly focus on the UGTs-mediated drug-drug and the effect of UGT1A genotype on the drug interactions of TKIs and explores strategies to address,aiming to provide clinicians and pharmacists with references for the safe and rational application of TKIs.

关 键 词：酪氨酸激酶抑制剂 尿苷二磷酸葡萄糖醛酸酶 药物相互作用 

分 类 号：R969.2[医药卫生—药理学]