肾移植受者红细胞内6-甲基巯基嘌呤核糖核苷酸(6-MMPR)浓度的影响因素研究  

Influencing Factors Analysis of 6-Methylmercaptopurine Ribonucleotides (6-MMPR) in Human Red Blood Cell (RBC) in Kidney Transplant Recipients

作　　者：师少军[1] 万景 杨春晓 周嘉黎 魏叶 黄希希 张蕊 刘亚妮[1] 曾繁典[2] SHI Shao-jun;WAN Jing;YANG Chun-xiao;ZHOU Jia-li;WEI Ye;HUANG Xi-xi;ZHANG Rui;LIU Ya-ni;ZENG Fan-dian(Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China;Institute of Clinical Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Hubei Wuhan 430030, China)

机构地区：[1]华中科技大学同济医学院附属协和医院药学部,武汉430022 [2]华中科技大学同济医学院临床药理研究所,武汉430030

出　　处：《中国药学杂志》2019年第10期803-808,共6页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金面上项目资助(81874326);湖北省自然科学基金面上项目资助(2017CFB761);国家重点研发计划资助(2017YFC0909900)

摘　　要：目的对服用硫唑嘌呤(AZA)的中国肾移植受者红细胞(RBC)内代谢物6-甲基巯基嘌呤核糖核苷酸(6-MMPR)进行监测及影响因素分析,为临床个体化用药提供参考。方法以100例中国肾移植受者为研究对象,应用已确证的HPLC-紫外法检测RBC内6-MMPR浓度,关联分析多种因素,包括患者年龄、性别、体重、AZA剂量和硫嘌呤甲基转移酶(TPMT)活性,对6-MMPR浓度的影响;并应用SPSS20. 0软件进行多元线性回归分析,考察6-MMPR浓度影响因素。结果 100例中国肾移植受者RBC内6-MMPR浓度呈非正态分布(P <0. 000 1),浓度范围为65. 75~10 616. 00 pmol·(8×108)-1RBC。关联分析与多元线性回归分析结果均表明,患者年龄、性别、体重、AZA剂量对6-MMPR浓度均无显著影响(P> 0. 05);而RBC内TPMT活性与6-MMPR浓度水平间呈显著正相关性(P <0. 001)。结论 RBC内TPMT活性是影响6-MMPR浓度的独立因素,进而影响该类药物临床疗效和毒性反应。OBJECTIVE To monitor and investigate the influencing factors of 6-methylmercaptopurine ribonucleotides (6-MMPR) in human red blood cell (RBC) in Chinese kidney transplant recipients treated with azathiopurine (AZA), and to provide references for clinical personalized medicine. METHODS In 100 Chinese kidney transplant recipients, the concentration of 6-MMPR in RBC was detected by validated HPLC-UV method. Correlation analysis was performed to analyze the effects of various factors, including patient age, gender, weight, AZA dose and thiopurine S-methyltransferase (TPMT) activity, on the 6-MMPR concentration, and multivariate linear regression analysis was performed using SPSS20.0 software to investigate the influencing factors of 6-MMPR concentration. RESULTS The concentration of 6-MMPR in 100 Chinese kidney transplant recipients was not normally distributed (P<0.000 1), and the concentration range was 65.75-10 616.00 pmol·(8×108)-1 RBC. Correlation analysis and multivariate linear regression analysis showed that age, gender, weight and AZA dose had no significant effect on 6-MMPR concentration (P>0.05), however, there was a significant positive correlation between TPMT activity and 6-MMPR concentration in RBC (P<0.001). CONCLUSION TPMT activity in RBC is an independent factor affecting 6-MMPR concentration, which in turn affects the clinical efficacy and toxicity of the drug.

关 键 词：肾移植受者 硫唑嘌呤(AZA) 6-甲基巯基嘌呤核糖核苷酸(6-MMPR) 影响因素 关联分析 多元线性回归分析 

分 类 号：R969[医药卫生—药理学]