CYP3A5不同基因型肾移植受者应用五酯胶囊对他克莫司谷浓度的影响  

Effects of Wuzhi capsules on tacrolimus concentration in renal transplant recipients with different CYP3A5 genotypes

作　　者：张恕芳 关紫菀 杜悦 张晓明[2] 李晓黎 吴坤荣 李妍[1] Zhang Shufang;Guan Ziwan;Du Yue;Zhang Xiaoming;Li Xiaoli;Wu Kunrong;Li Yan(Clinical Pharmacy,Shandong Provincial Qianfoshan Hospital,the First Hospital Affiliated with Shandong First Medical University,Jinan 250014,China;Department of Urology,Shandong Provincial Qianfoshan Hospital,the First Hospital Affiliated with Shandong First Medical University,Jinan 250014,China;College of Pharmacy,the First Hospital Affiliated with Shandong First Medical University,Tai’an 271000,China;College of Pharmacy,Shandong University,Jinan 250012,China)

机构地区：[1]山东第一医科大学第一附属医院(山东省千佛山医院)临床药学,济南250014 [2]山东第一医科大学第一附属医院(山东省千佛山医院)泌尿外科,济南250014 [3]山东第一医科大学药学院,泰安271000 [4]山东大学药学院,济南250012

出　　处：《中华泌尿外科杂志》2022年第4期279-284,共6页Chinese Journal of Urology

摘　　要：目的探讨CYP3A5不同基因型的肾移植受者应用五酯胶囊对他克莫司谷浓度的影响。方法回顾性分析2015年6月至2019年10月山东第一医科大学第一附属医院收治的162例首次行肾移植手术患者的病例资料。根据服用他克莫司期间是否联用五酯胶囊将患者分为联用组和未联用组。联用组和未联用组均为81例,男/女比例分别为62/19例和55/26例(P=0.219),年龄分别为(37.21±10.88)岁和(39.26±11.91)岁(P=0.103),体重分别为(66.18±13.89)kg和(62.39±11.64)kg(P=0.298),收缩压分别为(145.00±16.42)mmHg(1 mmHg=0.133 kPa)和(147.28±20.24)mmHg(P=0.276),舒张压分别为(92.20±12.53)mmHg和(92.25±13.87)mmHg(P=0.886),天冬氨酸转氨酶分别为(17.06±13.11)U/L和(12.24±8.59)U/L(P=0.015),丙氨酸转氨酶分别为(16.57±8.37)U/L和(17.76±9.12)U/L(P=0.463),空腹血糖分别为(7.18±2.74)mmol/L和(8.70±3.48)mmol/L(P=0.006),血红蛋白分别为(101.05±18.67)g/L和(98.96±17.53)g/L(P=0.789),肾移植术前肌酐分别为(797.32±279.82)μmol/L和(665.22±296.55)μmol/L(P=0.007),术前估计肾小球滤过率分别为(8.85±3.71)ml/(min·1.73m^(2))和(11.47±14.11)ml/(min·1.73m^(2))(P=0.130)。本研究162例中,CYP3A5*1*3基因型86例(53.09%),CYP3A5*1*1基因型17例(10.49%),CYP3A5*3*3基因型59例(36.42%),CYP3A5*1的最小等位基因频率为37.04%。联用组中,CYP3A5*1*3基因型47例(58.02%),CYP3A5*1*1基因型12例(14.81%),CYP3A5*3*3基因型22例(27.16%);未联用组中,CYP3A5*1*3基因型39例(48.15%),CYP3A5*1*1基因型5例(6.17%),CYP3A5*3*3基因型37例(45.68%),两组的基因型差异有统计学意义(P=0.024)。本研究162例均服用以他克莫司[首次剂量:0.15~0.30 mg/(kg·d)]为基础的三联免疫抑制方案(他克莫司+吗替麦考酚酯+糖皮质激素),联用组加用五酯胶囊(11.25 mg,2次/日)。采用酶联免疫法测定他克莫司谷浓度,比较两组间他克莫司谷浓度的差异,分析他克莫司谷浓度与CYP3A5基因型的相关性;比较联用组各基因型患�Objective To study the effect of Wuzhi capsules on tacrolimus trough concentration in kidney transplant recipients with different CYP3A5 genotypes.Methods From June 2015 to October 2019,162 patients who underwent renal transplantation for the first time were retrospectively analyzed.The patients were divided into two groups,combined and uncombined,according to whether combined with Wuzhi capsules.There were 81 cases in the uncombined group(55 males and 26 females),and 81 in the combined group(62 males and 19 females).There was no significant difference between the two groups(P=0.219).The ages of the uncombined group and the combined group were(39.26±11.91)years old and(37.21±10.88)years old(P=0.103),the weights were(62.39±11.64)kg and(66.18±13.89)kg(P=0.298),systolic blood pressure were(147.28±20.24)mmHg and(145.00±16.42)mmHg(1 mmHg=0.133 kPa)(P=0.276),diastolic blood pressure were(92.25±13.87)mmHg and(92.20±12.53)mmHg(P=0.886),alanine aminotransferase were(12.24±8.59)U/L and(17.06±13.11)U/L(P=0.015),aspartate aminotransferase were(17.76±9.12)U/L and(16.57±8.37)U/L(P=0.463),fasting blood glucose were(8.70±3.48)mmol/L and(7.18±2.74)mmol/L(P=0.006),hemoglobin were(98.96±17.53)g/L and(101.05±18.67)g/L(P=0.789),creatinine were(665.22±296.55)μmol/L and(797.32±279.32)μmol/L(P=0.007),estimated glomerular filtration rate were(11.47±14.11)ml/(min·1.73m^(2))and(8.85±3.71)ml/(min·1.73m^(2))(P=0.130)in the kidney transplant recipients before surgery.Among the 162 cases in this study,there were 86 cases(53.09%)of CYP3A5*1*3 genotype,17 cases(10.49%)of CYP3A5*1*1 genotype,59 cases(36.42%)of CYP3A5*3*3 genotype,and the minimum allele frequency of CYP3A5*1 was 37.04%.In the uncombined group,CYP3A5*1*3 genotype 39 cases(48.15%),CYP3A5*1*1 genotype 5 cases(6.17%),and CYP3A5*3*3 genotype 37 cases(45.68%).In the combined group,CYP3A5*1*3 genotype 47 cases(58.02%),CYP3A5*1*1 genotype 12 cases(14.81%),and CYP3A5*3*3 genotype 22 cases(27.16%),with statistically significant differences in the two groups(P=0.024).

关 键 词：肾移植 细胞色素P4503A5 基因多态性 五酯胶囊 肾移植受者 他克莫司 

分 类 号：R699.2[医药卫生—泌尿科学]