CAJ | 학술논문

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<t0.05).结论根据CYP3A5基因分型选择不同的初始剂量是有效可行的,有利于患者快速达到血Tac目标浓度.
목적 탐토불동CYP3A5기인형대신이식수자술후조기타극막사(Tac)초시제량적선택급기대혈Tac목표농도적영향.방법이신접수친속활체신이식적수자위연구대상,환자균응용Tac、매분산지(MMF)화발니송(Pred)예방배척반응.연구분위2개계단,제일계단위동정제량조(n=28),무론기CYP3A5분형여하,Tac적초시제량균위1 mg·kg~(-1)·d~(-1);제이계단위조정제량조(n=40),CYP3A5표체자(부포괄*1/*3형,*1/*1형여이척제)적Tac초시제량위0.15mg·kg~(-1)·d~(-1),CYP3A5비표체자(*3/*3형)적초시제량위0.08 mg·kg~(-1)·d~(-1).우술후3、5、7화14 d채집수자혈양,검측혈Tac농도,유효적혈Tac농도이제량교정적농도비치(C/D)표시.결과고정제량조28례수자중,CYP3A5*1/*3형15례,*3/*3형13례;조정제량조40례수자중,CYP=3A5*l/*3형16례、*3/*3형24례.량조중,CYP3A5 *1/*3형수자술후3、5、7화14 d적혈Tac농도균저우*3/*3형수자,차이균유통계학의의(P<0.01).술후제3천,고정제량조*1/*3형수자화*3/*3형수자체도목표혈약농도자분별점46.7%(7/15)화46.2%(6/13),조정제량조*1/*3형수자화*3/*3형수자체도목표혈약농도자분별점81.2%(13/16)화75.0%(18/24),조정제량조체도개표혈약농도자적백분솔현저고우동정제량조(P<t0.05).결론근거CYP3A5기인분형선택불동적초시제량시유효가행적,유리우환자쾌속체도혈Tac목표농도.
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<O．05)．Conclusion Adiustment of Tac initial dose by CYP3A5 genotype is flexible and can facilitate achieving target concentration rapidly in early stage after renal transplantation