Objective To investigate the role of polymorphism of cytochrome P450 CYP3A5 in determinationof initial tacrolimus（Tac）dosages and the influence on blood drug concentrations/dose（C/D）in early period afterrenal transplantation. Methods 157 patients transplanted with cadaver kidney were divided into expresser group（*1/*1 and *1/*3，n＝72），non-expresser group（*3/*3，n＝85）according to the CYP3A5 genotype. The Tac C/Dratio，the incidence of acute rejection and adverse reaction were compared between two groups. The initial dosage ofTac and the time needed to achieve first target tacrolimus blood concentration（7-14 μg/L）after transplantation in allof the different genotype patients were recorded. Results At 7，14 and 30 days after transplantation，the C/D ratioin the non-expresser group was significantly higher than that in the expresser group（all P＜0.05）；the difference ofthe ratio of acute rejection between two groups within 1 month was not significant（P＞0.05）；the adverse effects ofTac were increased in non-expresser group compared with expresser group within 1 month（P＜0.05）. The differenceof initial dosage of Tac between two group was not statistically significant（0.129，0.132 mg/kg respectively，P＞0.05）.However，the time needed to achieve first target TBC in expresser group was shorter than that in non-expresser（P＜0.05）. Conclusions To achieve target TBC rapidly and reduce the ratio of acute rejection and adverseeffects，the initial dosage of Tac for CYP3A5 *1/*1 & *1/*3 needs to be increased，and for CYP3A5 *3/*3 needs tobe decreased. Determined the initial dosage of Tac by CYP3A5 genotype is a way to reduce the ratio of acute rejectionand adverse effects of Tac and enhances the clinical effect of kidney transplantation.

Kidney transplantation, Tacrolimus, CYP3A5 genotype, CYP3A5 gene polymorphism

目的 观察 CYP3A5 基因多态性对肾移植受者术后早期他克莫司（tacrolimus，Tac）浓度 / 剂量比值（blood drug concentration/dose，C/D）的影响，探讨适合不同基因型受者的 Tac 起始剂量。方法 按CYP3A5 基因型将 157 例肾移植受者分为表达组（CYP3A5*1/*1 型和 CYP3A5*1/*3 型患者，72 例）、不表达组（CYP3A5*3/*3 型患者，85 例）。比较不同基因型患者之间术后 Tac C/D 比值、急性排斥反应与药物不良反应的发生率；记录不同基因型患者起始 Tac 剂量及达到肾移植术后早期有效目标药物浓度（7～14 μg/L）的间隔时间。结果 CYP3A5 表达组患者术后 7、14、30 天的 C/D 比值均低于不表达组（均 P＜0.05），术后 1 个月组间急性排斥反应发生率差异无统计学意义（P＞0.05），而不表达组药物不良反应发生率高于表达组（P＜0.05）；表达组及不表达组患者术后起始剂量无明显差异（分别为 0.129、0.132 mg/kg，P＞0.05）。但表达组患者达到目标浓度时间较不表达患者明显缩短（P＜0.05）。结论 受 CYP3A5 基因多态性影响，*1/*1 和 *1/*3 型患者早期要达到目标血药浓度，需提高该组患者的起始用药剂量，而 *3/*3 型患者则应适当降低起始剂量。根据 CYP3A5 基因多态性作为 Tac 个体化用药的依据，可以减少早期急性排斥反应及不良反应发生率，提高肾移植的临床效果。

肾移植 , 他克莫司 , CYP3A5 基因型 , CYP3A5 基因多态性