遗传多态性和临床药物会使人体重要药物代谢酶UGT1A1的表达和功能下降，会引发高胆红素血症及药源性毒性反应。盐酸埃克替尼是我国自主研发，具有知识产权的一种新型酪氨酸激酶抑制剂，具有很好的抗瘤效果，较好安全性和耐受性。其类似物尼洛替尼等可强烈抑制UGT1A1，使内源性胆红素及部分外源性药物代谢减缓，引起高胆红素血症及严重药物-药物相互作用（DDI）等不良反应发生。项目在前期发现埃克替尼可强烈抑制UGT1A1基础上，拟从体外、临床前和临床等多层面系统开展埃克替尼对UGT1A1的抑制效应研究，及基于不同遗传背景个体（UGT1A1突变人群）可能发生DDI的评估；并针对不同个体构建相应的DDI预测模型，探索一条利用药物对UGT1A1多态性的抑制特性，进而结合PPK手段预测药物在体内DDI发生的可能，为临床埃克替尼的个体化用药和DDI预警研究提供支持；同时，为临床转化医学的研究模式提供更多的实践经验

As a consequence, the patient has an increased risk of suffering from an adverse drug–drug interaction (DDI). Due to the clinical relevance of pharmacokinetic DDI mediated by drug-metabolizing enzymes, for example UDP-glucuronosyltransferase 1A1 (UGT 1A1), efficacy linked to dosage requirements and/or toxicity can be considered as appropriate endpoints. Although there were 63 UGT1A1 variants have been described, most are associated with absent, reduced, or inactive enzyme; UGT1A1*1 is associated with an normal enzyme level, UGT1A1*36 with an increased enzyme level, UGT1A1*28，UGT1A1*37，UGT1A1*6，UGT1A1*28 were associated with an decreased enzyme level, and the effects of some are unknown. So the UGT1A1 gene polymorphism, the suppressor gene polymorphism and UGT1A1 enzyme inhibitors were need attention, to prevent hyperbilirubinemia, liver toxicity and other adverse reactions occur very necessary..Icotinib{4-[(3-ethynylphenyl)amino]-6,7-benzo-12-crown-4-quinazoline hydrochloride} is a novel oral epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). It has independent intellectual property rights, In 2011, as a targeted anti-cancer drug to obtain CFDA approval for the listing in China. Data from clinical trial, show that icotinib have the antitumor activity in patients with advanced NSCLC and other solid tumors, and better safety and tolerability than other EGFR-TKIs. Common side effects included rash and diarrhea..No studies of formal drug interaction have been reported, the early literature suggests that the activity of UGT1A1 can be inhibited by the EGFR-TKIs class of drugs - including sorafenib, erlotinib, gefitinib and nilotinib, etc. However, so far, no reports of UGT1A1 activity was be inhibited by Icotinib, and no studies of inhibitory effect of different phenotypes UGT1A1 by EGFR-TKIs drug, especially Icotinib, and no reported of the inhibition effect produced DDI in Individuals with different genetic backgrounds..In a recent work, the project team found Icotinib for UGT1A1 showed a strong inhibitory activity; and the inhibition constant (Ki) values of Icotinib for 4-MU greater than the plasma concentration of it; DDI is based on the inhibition of UGT1A1 may occur in human. The project aims to investigate 1> the inhibition effect of UGT1A1 is by Icotinib in vitro; 2> the different inhibition effect of UGT1A1 in preclinical and clinical with different genetic backgrounds. From it, we can found the charaters of the Icotinib-UGT1A1 relationships, and predict the possible DDI based the UGT1A1 inhibition, and provide a theoretical and practice basis for the Icotinib in clinical medicine. Meanwhile, the study as a research model of medical clinical transformation, and the results of basic research transforming into clinically effective techniques and references can provide more practical experience.