CAJ | 학술논문

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（7～14μg/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。
목적관찰CYP3A5기인다태성대신이식수자술후조기타극막사（tacrolimus，Tac）농도/제량비치（blood drug concentration/dose，C/D）적영향，탐토괄합불동기인형수자적Tac기시제량。방법안CYP3A5기인형장157례신이식수자분위표체조（CYP3A5*1/*1형화CYP3A5*1/*3형환자，72례）、불표체조（CYP3A5*3/*3형환자，85례）。비교불동기인형환자지간술후Tac C/D비치、급성배척반응여약물불량반응적발생솔；기록불동기인형환자기시Tac제량급체도신이식술후조기유효목표약물농도（7～14μg/L）적간격시간。결과 CYP3A5표체조환자술후7、14、30천적C/D비치균저우불표체조（균P＜0.05），술후1개월조간급성배척반응발생솔차이무통계학의의（P＞0.05），이불표체조약물불량반응발생솔고우표체조（P＜0.05）；표체조급불표체조환자술후기시제량무명현차이（분별위0.129、0.132 mg/kg，P＞0.05）。단표체조환자체도목표농도시간교불표체환자명현축단（P＜0.05）。결론수CYP3A5기인다태성영향，*1/*1화*1/*3형환자조기요체도목표혈약농도，수제고해조환자적기시용약제량，이*3/*3형환자칙응괄당강저기시제량。근거CYP3A5기인다태성작위Tac개체화용약적의거，가이감소조기급성배척반응급불량반응발생솔，제고신이식적림상효과。
Objective To investigate the role of polymorphism of cytochrome P450 CYP3A5 in determination of initial tacrolimus(Tac)dosages and the influence on blood drug concentrations/dose(C/D)in early period after renal 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/D ratio,the incidence of acute rejection and adverse reaction were compared between two groups. The initial dosage of Tac and the time needed to achieve first target tacrolimus blood concentration(7-14μg/L)after transplantation in all of the different genotype patients were recorded. Results At 7,14 and 30 days after transplantation,the C/D ratio in the non-expresser group was significantly higher than that in the expresser group(all P<0.05);the difference of the ratio of acute rejection between two groups within 1 month was not significant(P>0.05);the adverse effects of Tac were increased in non-expresser group compared with expresser group within 1 month(P<0.05). The difference of 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 adverse effects,the initial dosage of Tac for CYP3A5*1/*1&*1/*3 needs to be increased,and for CYP3A5*3/*3 needs to be decreased. Determined the initial dosage of Tac by CYP3A5 genotype is a way to reduce the ratio of acute rejection and adverse effects of Tac and enhances the clinical effect of kidney transplantation.