Impact of MDR1 and CYP3A5 on the oral clearance of tacrolimus and tacrolimus-related renal dysfunction in adult living-donor liver transplant patients
Impact of MDR1 and CYP3A5 on the oral clearance of tacrolimus and tacrolimus-related renal dysfunction in adult living-donor liver transplant patients
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DOI：
10.1097/fpc.0b013e3282f9ac01
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发表时间：
2008-05-01
影响因子：
2.6
通讯作者：
Inui, Ken-ichi
中科院分区：
文献类型：
--
作者：
Fukudo, Masahide;Yano, Ikuko;Inui, Ken-ichi
目的探讨多药耐药1 （MDR1）基因和细胞色素P450 （CYP）基因CYP3A4和CYP3A5对成人活体肝移植患者他克莫司口服清除率（CL/F）的潜在影响。此外，还分析了肾功能障碍的发生与CYP3A5基因型的关系。方法对60例接受他克莫司治疗的新生成人肝移植患者进行研究。采用非线性混合效应建模程序，研究术后前50天各种协变量（包括移植时各组织中MDR1和CYP3A4的肠道和肝脏mRNA水平，以及CYP3A5*3多态性）对CL/F的影响。结果术后第14天CL/F呈线性增加，此后趋于稳定。肝移植后即刻初始CL/F受肠道MDR1 mRNA水平的显著影响(P
Objective The potential influence of the multidrug resistance 1 (MDR1) gene and the cytochrome P450 (CYP) genes, CYP3A4 and CYP3A5, on the oral clearance (CL/F) of tacrolimus in adult living-donor liver transplant patients was examined. Furthermore, the development of renal dysfunction was analyzed in relation to the CYP3A5 genotype.Methods Sixty de novo adult liver transplant patients receiving tacrolimus were enrolled in this study. The effects of various covariates (including intestinal and hepatic mRNA levels of MDR1 and CYP3A4, measured in each tissue taken at the time of transplantation, and the CYP3A5*3 polymorphism) on CL/F during the first 50 days after surgery were investigated with the nonlinear mixed-effects modeling program.Results CL/F increased linearly until postoperative day 14, and thereafter reached a steady state. The initial CL/F immediately after liver transplantation was significantly affected by the intestinal MDR1 mRNA level (P