多靶点酪氨酸激酶抑制剂治疗恶性肿瘤的群体药动学研究进展

Research Progress in Population Pharmacokinetics of Multiple Target Tyrosine Kinase Inhibitors in the Treatment of Malignant Tumors

多靶点酪氨酸激酶抑制剂是临床常用的抗肿瘤药物,其通过抑制细胞信号转导,从而促进肿瘤细胞凋亡,具有选择性高,副作用少的特点。目前在非小细胞肺癌、转移性肾癌、甲状腺癌及血液肿瘤等恶性肿瘤的治疗中应用广泛。但该类药物在临床疗效和药动学特征等方面受多种因素的影响,存在较大的个体差异。近年来,群体药动学研究发展迅速,广泛应用于多种药物的研究。笔者综述了阿昔替尼、伊马替尼、厄洛替尼和舒尼替尼在肿瘤患者及健康人群中的药动学特征及影响因素,进而对其群体药动学研究进展进行总结,分析了其在不同瘤种中的药动学特点及其相关协变量。结果表明,人口统计学因素、基因多态性、血生化指标、合并用药和肝肾功能是影响其在体内代谢的重要因素。试验设计和模型构建等因素可能是导致研究结果产生差异的重要原因。本文为临床制定合理、安全的个体化给药方案制定提供理论参考。

Multiple target tyrosine kinase inhibitors are commonly used in clinical as anti-tumor drugs,which can promote tumor cell apoptosis by inhibiting cell signal transduction,with high selectivity and few side effects.At present,it is widely used in the treatment of non-small cell lung cancer,metastatic renal cancer,thyroid cancer and hematological malignancies.However,the clinical efficacy and pharmacokinetic characteristics of these drugs are affected by many factors,and there are great individual differences.In recent years,the study of population pharmacokinetics is emerging and is widely used in the study of many drugs.In this paper,the pharmacokinetic characteristics and influencing factors of axitinib,imatinib,erlotinib and sunitinib in cancer patients and healthy people were summarized through the retrieval of relevant literature,and then the progress of pharmacokinetic research of tyrosine kinase inhibitors(TKIs)was reviewed.The pharmacokinetic characteristics in different tumor types were analyzed and the related covariates were summarized.The results showed that demographic factors,gene polymorphism,blood biochemical indexes,combined use of drugs and liver and kidney function were important factors affecting metabolism in vivo.Factors such as experimental design and model construction may be the important reasons for the differences in research results.The purpose of this study is to provide a reference for making a reasonable and safe drug therapy plan.