Influence of CYP3A5 and MDR1 (ABCB1) polymorphisms on the pharmacokinetics of tacrolimus in renal transplant recipients
Influence of CYP3A5 and MDR1 (ABCB1) polymorphisms on the pharmacokinetics of tacrolimus in renal transplant recipients
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DOI：
10.1097/01.tp.0000137789.58694.b4
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发表时间：
2004-10-27
期刊：
影响因子：
6.2
通讯作者：
Kato, T
中科院分区：
文献类型：
--
作者：
Tsuchiya, N;Satoh, S;Kato, T
背景基于体重的他克莫司剂量通常导致血药浓度的显著个体差异。他克莫司是细胞色素P450（CYP）3A 5和p-糖蛋白的底物，分别由CYP 3A 5和MDR 1（ABCB 1）编码，具有多个单核苷酸多态性。在本研究中，我们对CYP 3A 5 A6986 G、MDR 1 G2677（A/T）和C3435 T多态性进行了基因分型，并研究了这些多态性与他克莫司在肾移植受者中的药代动力学之间的关系。本研究入组了30名连续接受者。在移植后第28天分析他克莫司的药代动力学，此时将每日剂量调整至10-15 ng/mL的目标谷浓度。分别采用聚合酶链反应-限制性片段长度多态性和直接测序法对CYP 3A 5和MDR 1基因多态性进行分型。CYP 3A 5 *1携带者的他克莫司单次剂量/体重显著高于CYP 3A 5 *3/*3携带者（0.143 +/- 0.050 vs. 0.078 +/- 0.031 mg/kg，P
Background. A body-weight-based dose of tacrolimus often results in marked individual diversity of blood drug concentration. Tacrolimus is a substrate for cytochrome P450 (CYP) 3A5 and p-glycoprotein encoded by CYP3A5 and MDR1 (ABCB1), respectively, having multiple single nucleotide polymorphisms. In this study, we genotyped CYP3A5 A6986G, MDR1 G2677(A/T), and C3435T polymorphisms and investigated the association between these polymorphisms and the pharmacokinetics of tacrolimus in renal transplant recipients.Methods. Thirty consecutive recipients were enrolled in this study. The pharmacokinetics of tacrolimus was analyzed on day 28 after transplant, when the daily dose was adjusted to the target trough level of 10-15 ng/mL. The polymerase chain reaction-restriction fragment length polymorphism and direct sequence method were used for genotyping the CYP3A5 and MDR1 polymorphisms, respectively.Results. The single tacrolimus dose per body weight was significantly higher in CYP3A5 *1 carriers than CYP3A5 *3/*3 carriers (0.143 +/- 0.050 vs. 0.078 +/- 0.031 mg/kg, P