CYP3A5基因型对肾移植受者术后早期血他克莫司浓度的影响

目的 探讨不同CYP3A5基因型对肾移植受者术后早期他克莫司(Tac)初始剂量的选择及其对血Tac目标浓度的影响.方法以新接受亲属活体肾移植的受者为研究对象,患者均应用Tac、霉酚酸酯(MMF)和泼尼松(Pred)预防排斥反应.研究分为2个阶段,第一阶段为同定剂量组(n=28),无论其CYP3A5分型如何,Tac的初始剂量均为1 mg·kg~(-1)·d~(-1);第二阶段为调整剂量组(n=40),CYP3A5表达者(仅包括*1/*3型,*1/*1型予以剔除)的Tac初始剂量为0.15mg·kg~(-1)·d~(-1),CYP3A5非表达者(*3/*3型)的初始剂量为0.08 mg·kg~(-1)·d~(-1).于术后3、5、7和14 d采集受者血样,检测血Tac浓度,有效的血Tac浓度以剂量校正的浓度比值(C/D)表示.结果固定剂量组28例受者中,CYP3A5*1/*3型15例,*3/*3型13例;调整剂量组40例受者中,CYP=3A5*l/*3型16例、*3/*3型24例.两组中,CYP3A5 *1/*3型受者术后3、5、7和14 d的血Tac浓度均低于*3/*3型受者,差异均有统计学意义(P<0.01).术后第3天,固定剂量组*1/*3型受者和*3/*3型受者达到目标血药浓度者分别占46.7%(7/15)和46.2%(6/13),调整剂量组*1/*3型受者和*3/*3型受者达到目标血药浓度者分别占81.2%(13/16)和75.0%(18/24),调整剂量组达到开标血药浓度者的百分率显著高于同定剂量组(P

The effects of polymorphism of cytochrome P450 CYP3A5 on the initial concentration of blood tacrolimus in recipients after renal transplantation

Objective To investigate the role of polymorphism of cytochrome P450 CYP3A5 in determination of initial tacrolimus(Tac)dosages and the influence on trough concentrations in early period after renal transplantation．Methods All the cases received relative living renal transplantation de novo and immunosuppressive protocol was Tac+MMF+ prednisone．The study was conducted in 2 successive stages：in stage 1 (dosage-fixed group，n=28)，fixed tac initial dose 0．1 mg·kg~(-1)·d~(-1) was administered to the recipients regardless of CYP3A5 genotypes；in stage 2(dosage-adjusted group，n=40)，the adjusted Tac initial dosages based on CYP3A5 genotype for the expressers(only CYP3A5*1／*3 included，and those with CYP3A5*1／*1 were excluded)and non-expressers (CYP3A5*3／*3)were 0．15 mg·kg~(-1)·d~(-1) and 0．08 mg·kg~(-1)·d~(-1)，respectively．The blood samples were drawn from patients for Tac level measurement on the 3rd，5th，7th and 14th day post-operation，and concentration-to-adjusted dose ratio(C／D ratio)was used to indicate the tested drug level．Results In the dosage-fixed group，there were 15 cases carrying CYP3A5*1／*3 and 13 carrying CYP3A5 *3／*3．In the dosage-adjusted group，there were 16 cases carrying CYP3A5*1／*3 and 24 carrying CYP3A5*3／*3．In two groups，C／D ratio among recipients with CYP3A5*1／-16 3 was all markedly lower than that with CYP3A5*3／*3(both P<0．05)at different time points(Day 3，5，7，14)．46．7 0A(7／15)cases carrying CYP3A5*1／*3 and 46．2%(6／13)carrying*3／*3 achieved target blood tacrolimus concentration in the fixed-dosage group，while 81．2%(13／16)，and 75．0%(18／24) carrying CYP3A5*1／*3 and*3／*3 reached target concentration in the dosage-adjusted group，respectively．The percentages of different CYP3A5 genotype carriers reaching target concentration in the dosage-adjusted group were all markedly higher than those in the dosage-fixed group(P