吉西他滨的核苷酸转运体基因组学研究  

Study on the genomics of nucleoside transporters of gemcitabine

作　　者：楼江[1,2] 林能明[1,2] 王刚[1,2] 王飞[1,2] 李晴宇[1,2] 史长城[1,2] 严伟[1,2] 

机构地区：[1]杭州市第一人民医院药学部 [2]南京医科大学附属杭州医院药学部

出　　处：《中国临床药理学与治疗学》2016年第5期586-594,共9页Chinese Journal of Clinical Pharmacology and Therapeutics

摘　　要：吉西他滨是胰腺癌、非小细胞肺癌和膀胱癌等癌症的一线化疗药物,但个体化差异较大,有效率仍偏低,粒细胞减少症和血小板减少症等血液系统毒性是吉西他滨临床应用的主要挑战,这可能与吉西他滨和体内活性代谢物三磷酸核苷的浓度有关。核苷酸转运体是吉西他滨摄取入细胞的内吞转运体,也是吉西他滨发挥细胞毒的关键步骤,它的基因突变可能影响转运体的表达和活性,进而影响吉西他滨个体间的药代动力学和临床疗效。因此本文就核苷酸转运体基因多态性与接受吉西他滨治疗患者的药动学及药效学相关性进行阐述。Gemcitabine is used as a first-line chemotherapeutic agent for the treatment of various carcinomas including pancreatic cancer,non-smallcell lung cancer and bladder cancer.But high interindividual variability,low response rate and adverse effects including granulocytopenia and thrombocytopenia have been the major challenges faced by clinicians,which maybe associated with the gemcitabine and active metabolite gemcitabine triphosphate pharmacokinetics.Gemcitabine is transported into cells by nucleoside transporters,which serves an important role in gemcitabine efficacy.The allele frequencies of nucleoside transporters gene variants could influence their expression and activity and thus contributing to interindividual variability in gemcitabine pharmacokinetics as well as treatment response.This paper discusses single nucleotide polymorphisms of nucleoside transporters associated with gemcitabine pharmacokinetics and pharmacodynamics in solid tumors patients.

关 键 词：吉西他滨 核苷酸转运体 基因多态性 药代动力学 药效学 

分 类 号：R733[医药卫生—肿瘤]