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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。
Objective To investigate the effects of C1236T, G2677T / A and C3435T polymorphisms of cytochrome P450 enzyme 3A5 (CYP3A5) gene and multidrug resistance gene (MDR1) on the pharmacokinetics of Tacrolimus in patients after liver transplantation . Methods Blood samples were collected from 28 patients with liver transplantation at the first week and the third week after operation. The plasma concentrations of TAC were measured by LC-MS / MS and the main pharmacokinetic parameters were calculated. The major genotypes of CYP3A5 * 3 and MDR1 in 28 patients with liver transplantation were analyzed by polymerase chain reaction and gene sequencing. Results After oral administration of TAC, the pharmacokinetic parameters AUC0 → t and ρmax of patients with MDR1 3435T genotype were significantly higher than those of patients with genotype 3435CC. The polymorphisms of CYP3A5 * 3, MDR1 C1236T and G2677T / Learning parameters no significant effect. Conclusion MDR1 3435 T genotype liver transplantation requires a higher dose than the 3435 CC genotype to achieve the target concentration.