摘要
目的探讨CYP3A5*3基因多态性对肾移植术后他克莫司(免疫抑制药)剂量校正给药2h后浓度的影响。方法选取61例肾移植术后患者,用聚合酶链式反应-限制性片段长度多态性的方法,分析CYP 3A5*3基因型;用微粒酶联免疫吸附法,测定患者他克莫司浓度。并分析CYP 3A5*3基因多态性与他克莫司给药剂量、给药2h浓度(C2)及剂量校正给药2h后浓度(C2/D)的相关性。结果肾移植术后1周及1、3个月,CYP 3A5*1/*1+CYP 3A5*1/*3组和CYP3A5*3/*3组他克莫司剂量比较均无显著性差异。术后1周和1个月,2组间他克莫司C2比较无显著性差异;术后3个月,CYP 3A5*1/*1+CYP 3A5*1/*3组的C2显著低于CYP 3A5*3/*3组(P<0.05)。术后1周及1、3个月,CYP 3A5*1/*1+CYP 3A5*1/*3组的C2/D均明显低于CYP 3A5*3/*3组(P<0.05)。结论肾移植术后,他克莫司C2/D的个体化差异与患者CYP3A5*3基因型密切相关。
Objective To investigate the association between CYP 3A5 ＊ 3 genetic polymorphism and tacrolimus dose -adjusted concentration at 2 hours after administration （ C2/dose）. Methods CYP 3A5＊3 genotype were analyzed by polymerase chain reaction restriction length polymorphism in 61 Chinese renal transplant recipients fragment receiving tacrolimus. Microparticle enzyme immunoassay was used to measure the whole blood concentration of tacrolimus. Tacrolimus dose were determined at 1 week, 1 month, and 3 months after transplantation. Results There was no significant difference of taerolimus dosage between CYP 3A5 ＊ 1/＊ 1 ＋ CYP 3A5 ＊ 1/＊ 3 group and CYP 3A5 ＊ 3/ ＊ 3 group. At 1 week and 1 month after transplantation, taerolimus C2 did not show significant difference between the two groups, while at 3 months after transplantation, C2 of CYP 3A5 ＊ 1/＊ 1 ＋ CYP 3A5 ＊ 1/＊ 3 group and is significantly lower than the CYP 3A5 ＊ 3/＊ 3 group（P 〈 0.05）.C2/dose ofCYP3A5＊1/＊1 ＋ CYP3A5＊ 1/.3 group at 1 week, 1 month and 3 months after transplantation were significantly lower than CYP 3 A5 ＊ 3/＊ 3 group （P 〈 0.05 ）. Conclusion In renal transplantation, the taerolimus C2/dose was associated with the CYP 3A5 ＊ 3 genetic polymorphism.
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2008年第3期207-211,共5页
The Chinese Journal of Clinical Pharmacology
基金
国家自然科学基金资助项目(30371668)
