摘要
目的探究肾移植术后1个月内使用缓释剂型他克莫司（Tac-QD）及普通剂型他克莫司（Tlac-BID）在不同CYP3A5基因型受者的血他克莫司浓度变化特点及受者预后情况。方法回顾性分析106例服用Tae-QD或Tac-BID肾移植受者的临床资料，检测术后28d内受者血他克莫司浓度谷值及CYP3A5基因型。根据基因型分为表现型（CYP3A5＊1／3和CYP3A5＊1／1）及非表现型（CYP3A5＊3／3）。比较服用不同剂型、不同表现型等各组受者间术后28d内血他克莫司浓度、他克莫司剂量及浓度剂量比值（C／D值）的变化，以及达到血他克莫司目标浓度受者的比例。分析C／D值的影响因素及血他克莫司浓度和C／D值的变异系数。观察术后1年的随访情况。结果术后第14、21和28d时，Tac-QD组受者他克莫司用量均明显高于Tat-BID组（P〈0．01），术后第5、7、14和21d时，Tae-QD组受者的血他克莫司浓度较低（P〈0．05），而术后第28天时Tac-QD组血他克莫司浓度明显高于Tae-BID组（P〈0．01）。Tac-QD组非表现型受者术后第7、21、28天的血他克莫司浓度明显高于表现型受者（P〈0．05）。Tae-BID组表现型受者术后第5天后他克莫司用量明显高于非表现型受者（P〈0．05），而术后1个月内Tac-BID组表现型受者血他克莫司浓度明显低于非表现型受者（P〈0．05）。术后各检测时点非表现型组受者血他克莫司浓度均明显高于表现型组受者（P〈0．01）。术后3d，CYP3A5非表现型受者的C／D值均明显高于表现型受者（P〈0．05）。术后5～21d，非表现型组中使用Tac-BID者的C／D值均明显高于使用Tac-QD者及所有cYP3A5表现型受者（P〈0．05）。术后28d，非表现型组受者中使用Tac-QD者的C／D值较使用Tac-BID者出现明显升高（P〈0．01）。术后第5和7天，CYP3A5非表现型受者中使用Tac-BID者达到血他克莫司目标浓度的受者比例分别为84％和77．78％
Objective To explore the characteristics of blood concentration and prognosis of one year follow-up in low- and high-express cytochrome P450 3A5 recipients receiving once- or twice-daily Tacrolimus （Tac-QD, Tac-BID）. Method We retrospectively collected 28-day results of blood concentration, dosage and factors that might influence blood concentration of Tacrolimus in de novo kidney transplantation repicients from May 2013 to June 2014 receiving Tac-QD or Tac-BID. The expression of cytochrome P450 3A5 genetic polymorphism was detected, and classified as low-express （CYP3A5 ＊ 3 ＊ 3） and high-express （CYP3A5 ＊ 1 ＊ 3, CYP3A5 ＊ 1 ＊ 1）. The prognoses of one year follow-up were also recorded and compared. Result It was found that 40 （37. 7%） out of 106 kidneytransplant recipients had the low-express genotype （CYP3A5＊3/＊3）. Twenty-one days after transplantation, higher dose of Tac-QD was needed for increasing blood concentration （P〈0. 01）. In low-express patients, it was more difficult to increase blood coneentration of Tacrolimus in recipients receiving Tac-QD than Tat-BID. The low-express patients taking Tac-BID was found easier to achieve target concentration at 7th day after transplantation （P〈0. 01 ）. Dose-normalized trough level of tacrolimus （C/D） had a correlation with expressing type within 7 days and dosage on the day 7 to 28 （P〈0. 01）. There was no significant difference in coefficient of variation of concentration and C/D between the two forms of drugs. There was no significant difference in one-year survival rate of patients and allografts between Tac-QD and Tac-BID. The infection rate was higher in low-express patients treated with Tac-QD （P〈0. 05）. Conclusion Low-express patients receiving Tac-BID were easier to increase blood concentration and achieve target concentration of Tacrolimus. The infection rate in low-express patients receiving Tac-QD was high. The early stage treatment with Tat-BID after transplantation is recommended in low-expres
出处
《中华器官移植杂志》
CAS
CSCD
2015年第8期458-464,共7页
Chinese Journal of Organ Transplantation
