CYP3A5基因多态性对膜性肾病患者他克莫司血药浓度影响的研究  

Study of Effect on the Blood Concentration of Tacrolimus in the Membranous Nephropathy Patients with CYP3A5 Gene Polymorphism

作　　者：蔺婷婷 魏传梅[1] 孙绍伟[1] LIN Ting-ting;WEI Chuan-mei;SUN Shao-wei(Department of Pharmacy Binzhou Medical University Hospital,Binzhou 256603,China)

机构地区：[1]滨州医学院附属医院药学部

出　　处：《海峡药学》2019年第11期115-118,共4页Strait Pharmaceutical Journal

基　　金：山东省医药卫生科技发展计划(No.2017WS041);滨州医学院科研计划与科研启动基因项目(No.BY2014KJ57);山东省药学会临床药学奥赛康中青年科研资助项目(No.Sdpa-ask-2014-03)

摘　　要：目的通过回顾性分析,研究细胞色素P450(CYP)3A5基因分型对他克莫司用于治疗膜性肾病(Membranous nephropathy,IMN)患者的血药浓度的影响。方法收集66例IMN患者信息。采用酶放大免疫测定法(EMIT)监测其全血血药浓度。利用荧光染色原位杂交测序(FISH)检测系统确定基因型,根据不同基因型对患者进行分组。观察3组患者在治疗前后的尿蛋白、白蛋白以及血肌酐等指标的变化。结果通过他克莫司血药浓度/剂量×体表面积(C/D′)值可以看出,CYP3A5*1/*1型和*1/*3型患者他克莫司的C/D′值显著性低于*3/*3型患者。结论临床上,患者在服用他克莫司前进行CYP3A5基因型检测,预测他克莫司用药剂量,CYP3A5*1/*1型和*1/*3型基因型患者需要服用更大的剂量才能维持在有效血药浓度范围内,这样有助于提高他克莫司应用的安全性和有效性。OBJECTIVE To retrospective analyze the effect of CYP3A5 genotyping on the blood concentration of tacrolimus in the membranous nephropathy patients.METHODS A total of 66 membranous nephropathy patients were collected in our study.Enzyme-multiplied immunoassay technique(EMIT)was utilized to determine the serum tacrolimus valley concentrations.The fluorescence in situ hybridization(FISH)technology was used to detect the CYP3A5 gene polym orphisms in all the patients.According to the different genotypes,the patients were divided into different groups.RESULTS The C/D′ratio of tacrolimus in patients with CYP3A5*1/*1 and*1/*3 genotype group were significantly lower than those with CYP3A5*3/*3 genotype groups.CONCLUSION Detection of CYP3A5genotype has potential to estimate the tacrolimus dosage which is useful to improve the safety and effectivity of tacrolimus therapy.The CYP3A5*1/*1 and*1/*3 genotype patients need higher dose of tacrolimus clinically to achieve the perfect concentration.

关 键 词：他克莫司 膜性肾病 血药浓度 基因多态性 

分 类 号：R969.4[医药卫生—药理学]