CYP3A5和MDR1基因多态性对中国肝移植患者他克莫司药动学的影响  

Influence of genetic polymorphism of CYP3A5 and MDR1 on the pharmacokinetics of tacrolimus in Chinese liver transplantation patients

作　　者：刘晓雪[1] 陈冰[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院药剂科,上海200025

出　　处：《中国临床药学杂志》2014年第5期283-287,共5页Chinese Journal of Clinical Pharmacy

摘　　要：目的探讨细胞色素P450酶3A5(CYP3A5)基因和多药耐药基因(MDR1)C1236T、G2677T/A、C3435T多态性对肝移植患者口服他克莫司(TAC)后体内药动学参数的影响。方法采集28例肝移植患者手术后第1周和第3周血标本,采用LC-MS/MS法检测TAC血药浓度,计算主要药动学参数。采用聚合酶链反应结合基因测序分析28例肝移植患者CYP3A5*3和MDR1主要基因型。结果携带MDR1 3435T基因型的肝移植患者口服TAC后,药动学参数AUC0→t和ρmax明显高于3435CC型患者,而CYP3A5*3、MDR1 C1236T和G2677T/A基因多态性对TAC的药动学参数无明显影响。结论携带MDR1 3435 T基因型肝移植患者比3435 CC型患者需要较高剂量才能达到目标浓度。AIM To investigate the infltence of CYP3A5＊3 and MDR1 C1236T, G2677T/A and C3435T genotypes on tacrolimus （TAC） pharmacokinetics in Chinese liver transplant recipients. METHODS The blood samples of 28 patients were collected after 1 week and 3 weeks therapy of TAC after liver transplantation. The TAC concentration in whole blood was measured by LC-MS/MS. The pharmacokinetic parameters were calculated. Polymerase chain reaction and gene sequencing were used for CYP3A5 ＊ 3 and MDR1 genotyping in 28 patients. RESULTS The dose- and weight- adjusted peak concentration （ρmax） and area under the concentration-time curve （AUC0→1） were significantly higher in patients carrying MDRI 3435T allele than 3435CC patients. CYP3A5 ＊3, MDR1 C1236T and G2677T/A genotypes did not affect TAC pharmacokinetic parameters. CONCLUSION Liver transplant recipients with MDR1 3435CC may require higher dose of TAC than 3435T carriers.

关 键 词：他克莫司 药动学 肝移植 MDR1 CYP3A5 基因多态性 

分 类 号：R96[医药卫生—药理学]