克唑替尼相关肝损伤研究进展  

Research progress of liver injury induced by crizotinib

作　　者：程军[1] 韩一萱[1] 汪龙[1] 朱玲娜[1] Cheng Jun;Han Yixuan;Wang Long;Zhu Lingna(Department of Pharmacy,the Third People′s Hospital of Bengbu,Anhui Province,Bengbu 233000,China)

机构地区：[1]安徽省蚌埠市第三人民医院药学部,蚌埠233000

出　　处：《药物不良反应杂志》2023年第2期107-111,共5页Adverse Drug Reactions Journal

摘　　要：克唑替尼是一种作用于间变性淋巴瘤激酶(ALK)、细胞间质表皮转化因子及c‑ros肉瘤致癌因子1(ROS1)的多靶点小分子酪氨酸激酶抑制剂,临床主要用于治疗ALK阳性和/或ROS1阳性的晚期非小细胞肺癌。肝损伤是克唑替尼十分常见的不良反应之一,多数患者表现为无临床症状的转氨酶水平升高,极少数患者可出现致命性肝衰竭;发生机制与线粒体介导的细胞凋亡和过度自噬、氧化应激、过敏反应等有关。克唑替尼相关肝损伤的危险因素包括既往肝病史,乙型肝炎病毒感染,联合使用免疫检查点抑制剂或H_(2)受体拮抗剂/质子泵抑制剂,以及信号转导与转录激活因子1和细胞色素P450基因多态性等。应用克唑替尼前,须对患者肝功能进行综合评估,治疗过程中加强监测,必要时采取暂时(再次使用时减量)或永久停药等措施。Crizotinib is a multi‑target small molecule tyrosine kinase inhibitor,which can act on anaplastic lymphoma kinase(ALK),cellular‑mesenchymal to epithelial transition factor and c‑ros oncogene 1(ROS1).It is mainly used in patients with ALK/ROS1‑positive advanced non‑small cell lung cancer.Liver injury is one of the most common adverse reactions of crizotinib.The typical symptom of crizotinib‑induced liver injury is asymptomatic aminotransferase elevation,and fatal liver failure can occur in very few patients.The mechanism is mainly related to mitochondrial‑mediated apoptosis,excessive autophagy,oxidative stress,and anaphylaxis.The risk factors involved are history of liver diseases,hepatitis B virus infection,com‑bined use of immune checkpoint inhibitors or H_(2)‑antagonist/proton pump inhibitor,gene polymorphisms of signal transducer and activator of transcription 1 and cytochrome P450.It is very important to assess liver function comprehensively before treatment,and strengthen the therapeutic drug monitoring during treatment.Measures such as temporary(reduce the dose when re‑use)or permanent discontinuation should be taken when necessary.

关 键 词：酶抑制剂 肝 药物毒性 化学和药物性肝损伤 克唑替尼 酪氨酸激酶抑制剂 

分 类 号：R969.3[医药卫生—药理学]