摘要
多发性骨髓瘤（MM）是常见的血液系统恶性肿瘤，随着硼替佐米等新药的推广应用，MM患者的预后得到极大改善。但是仍有部分MM患者接受新药治疗后疗效较差，除肿瘤负荷、肿瘤生物学特性的差异之外，不同患者的药物代谢动力学水平的差异，亦可引起药物体内暴露的不同，进而影响疗效，并且导致不良反应的发生。由于需要治疗合并症和预防化疗所致不良反应，MM患者可能需要同时接受多种药物的治疗，在评价药物疗效和不良反应时，药物相互作用（DI）越来越多地引起基础医学研究者和临床医师的重视。肝微粒体内细胞色素P450酶（CYP）作为重要的药物Ⅰ相代谢酶，是DI敏感性的主要影响因素之一。因此，基于治疗MM的一线药物硼替佐米的多药治疗，笔者拟就MM患者的DI，CYP3A4和CYP2C19等常见CYP基因多态性及其对硼替佐米代谢影响的研究进展进行综述。
Multiple myeloma （MM） is a common hematological malignancy. As the emergence of novel therapies such as bortezomib, the prognosis of MM patients has acquired great improvement. But still, the outcomes of some MM patients receiving the novel therapies are poor. Besides the differences of burden and biological aspects of tumors, the differences of levels of individual pharmacokinetic parameters may cause different drug exposure and clinical outcomes. On the other side, a patient may receive several drugs in order to prevent against adverse reactions and complications of chemotherapy. More and more scholars and doctors increasingly pay attention to the drug interaction （DI） when they evaluate the clinical outcomes of the drugs. As an important metabolic enzyme in phase Ⅰ, cytochrome P-450 enzyme （P450） is one of the main influence factors of DI sensitivity. This article focuses on multidrug therapy based on the first-line drug bortezomib of MM, the DI during the phase of drug metabolism in MM patients, the effect of DI, common genetic polymorphism of CYP2C19 and CYP3A4 on the drug metabolism, especially the metabolism of bortezomib are reviewed.
作者
冷亚美
张陆阳
许琳
潘崚
张丽
Leng Yamei;Zhang Luyang;Xu Lin;Pan Ling;Zhang Li(Department of Hematology,West China Hospital,Sichuan University,Chengdu 610041,Sichuan Province,China;Department of Orthodontics,West China Hospital of Stomatology,Sichuan University,Chengdu 610041,Sichuan Province,China)
出处
《国际输血及血液学杂志》
CAS
2018年第5期424-430,共7页
International Journal of Blood Transfusion and Hematology
基金
中国抗癌协会血液肿瘤科研发展基金（312160342）
国家自然科学基金（81770218）
