CYP3A5基因型对肾病综合征患者他克莫司血药浓度与剂量比的影响  

Effect of CYP3A5 genotype on the concentration/dose ratio of tacrolimus to nephrotic syndrome patients

作　　者：叶冬梅[1] 刘晓霞[1] 兰顺[1] 王金泉[2] 

机构地区：[1]广西壮族自治区人民医院,广西南宁530021 [2]桂林医学院药学系,广西桂林541004

出　　处：《中国医院药学杂志》2014年第24期2139-2143,共5页Chinese Journal of Hospital Pharmacy

基　　金：广西医疗卫生重点科研课题(编号:桂卫重2012105)

摘　　要：目的:研究CYP3A5基因型对肾病综合征患者他克莫司血浓度与剂量比值(C/D)的影响。方法:选取2012年5月-2014年月1月诊断为肾病综合征的60例患者,测定用药后1,2,3,4,8,12周的他克莫司血谷浓度,计算C/D比值,根据尿蛋白、血浆白蛋白、水肿程度及肾功能进行临床疗效评价。检测患者CYP3A5基因型,分析基因型与C/D比值的关系。结果:在60例患者中,7例CYP3A5*1/*1型,占11.67%;29例CYP3A5*1/*3型,占48.33%;24例CYP3A5*3/*3型,占40.00%。治疗后1,2,3,4,8,12周他克莫司C/D比值顺序依次为:CYP3A5*1/*1型<CYP3A5*1/*3型<CYP3A5*3/*3型,差异有统计学意义(P<0.05)。结论:患者接受他克莫司治疗后C/D比值与CYP3A5基因型具有相关性。CYP3A5*1/*1型和CYP3A5*1/*3型患者需要比CYP3A5*3/*3型患者服用更高剂量的他克莫司才能达到相同的血浓度。用药前检测受者基因型可更合理的制定他克莫司给药方案。OBJECTIVE Study on the effect of CYP3A5 genotype on the concentration/dose （C/D） ratio of tacrolimus in nephrotic syndrome patients. METHODS Sixty nephrotic syndrome patients received tacrolimus treatment from May 2012 to January 2014 were selected. The blood valley concentration of tacrolimus was ditected after taking medicine at 1,2,3,4, 8 andl2 weeks respectively, and the C/D ratio was calculated, the therapeutic efficacy was ohservatived according to urine protein, plasma albumin, edema degree and renal function. The CYP3A5 genotypes were determined, and the relationship between Tacrolimus C/D ratio and genotype was evaluated by SPSS 16. 0. RESULTS The number of CYP3A5 ＊ 1/＊ 1, ＊ 1/＊ 3 and ＊ 3/＊ 3 allelic gene was 7 （11. 670//00 ）, 29 （48. 330//00 ）, and 24 （40. 00% ）. The tacrolimus C/D ratios size order of allelic gene was CYP3A5 ＊ 1/＊ 1%CYP3A5 ＊ 1/＊ 3 〈CYP3A5 ＊ 3/＊ 3 at 1,2,3,4,8,12 weeks after taking medicine （P〈0. 05）. CONCLUSION The Tacrolimus C/D ratios is correlated to the CYP3A5 genotype intimately in nephrotic syndrome patients . The patients with CYP3A5 ＊ 1 allelic genes need higher dose of tacrolimus to achieve the perfect concentration. Genotype detection of CYP3A5 will provide a scientific basis for rational use of tacrolimus in nephrotic syndrome patients.

关 键 词：肾病综合征 CYP3A5酶 他克莫司 基因型 

分 类 号：R966[医药卫生—药理学]