| 环孢素注射液在肾移植患者中的血药浓度与基因多态性的相关性研究 |
| 投稿时间：2019-11-25 修订日期：2020-03-16 点此下载全文 |
| 引用本文：张艳霞,陈泉金,宋洪涛.环孢素注射液在肾移植患者中的血药浓度与基因多态性的相关性研究[J].药学实践杂志,2020,38(4):334~339 |
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| 中文摘要:目的 观察环孢素注射液在肾移植患者亚临床或临界排斥反应治疗中的临床疗效，研究与环孢素药动学相关的9个单核苷酸多态性（SNPs）和环孢素注射液剂量校正谷浓度（C0/D'）的相关性，建立环孢素注射液的个体化给药模型。方法 收集并记录144例使用环孢素注射液的成年肾移植患者的血液样本及临床资料，对患者的CYP3A4*18B、CYP3A5*3、ABCB1(C1236T、G2677T/A、C3435T)、POR*28、PXR(C5705T、C39823T)以及NFKB1-94 ins/del ATTG等9个SNPs进行基因分型，比较不同基因型患者之间C0/D'的差异，并应用多重回归分析方法建立基于基因多态性的个体化给药方案。结果 环孢素注射液可使68.8%发生亚临床或临界排斥反应的肾移植患者血肌酐水平得到改善，稳态血药浓度为（189.50±38.56）ng/ml。CYP3A4*18B基因多态性与环孢素注射液的C0/D'具有显著相关性，*1/*1基因型患者的C0/D'显著高于*18B/*18B基因型患者；CYP3A5*3、ABCB1 （C1236T、G2677T/A、C3435T）、PXR（C5705T、C39823T）、NFKB1-94 ins/del ATTG及POR*28基因多态性均与环孢素注射液的C0/D'无显著相关性。在最终回归模型中，血红蛋白和CYP3A4*18B基因多态性与环孢素注射液C0/D'显著相关。结论 环孢素注射液可有效改善发生亚临床或临界排斥反应的肾移植患者的血肌酐水平；CYP3A4*18B基因多态性与环孢素注射液的C0/D'显著相关。 |
| 中文关键词:肾移植 环孢素注射液 基因多态性 CYP3A4 个体化给药 |
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| Study on correlation between plasma concentration of cyclosporine injection and gene polymorphism in renal transplant patients |
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| Abstract:Objective To investigate the clinical efficacy of cyclosporine injection in subclinical or critical treatment of renal transplant patients，and to establish an individualized dosage regimen of cyclosporine injection by studying the effects of nine single nucleotide polymorphisms related to the pharmacokinetics of cyclosporine on the dose-adjusted trough concentration (C0/D') of cyclosporine injection.Methods Blood samples and clinical data of 144 adult renal transplant patients who used cyclosporine injection were collected and recorded, then, their genotypes of CYP3A4*18B, CYP3A5*3, ABCB1 (C1236T, G2677T/A, C3435T), POR*28, PXR (C5705T, C39823T) and NFKB1-94 ins/del ATTG were determined by Sequenom MassARRAY® SNP methods. Then, the discrepancies of cyclosporine injection’s C0/D' among the patients with different genotypes was compared and an individualized dosage regimen based on gene polymorphism of cyclosporine injection was established by using multivariate regression analysis.Results Cyclosporine injection improved serum creatinine level by 68.8% in renal transplant patients with subclinical or critical rejection, and the steady-state plasma concentration was (189.50±38.56) ng/ml. The CYP3A4*18B gene polymorphism was significantly correlated to C0/D' of cyclosporine injection, and the C0/D' of patients with *1/*1 genotype was significantly higher than patients of *18B/*18B genotype; but CYP3A5*3, ABCB1(C1236T, G2677T/A, C3435T), PXR C5705T, PXR C39823T, NFKB1-94 ins/del ATTG and POR*28 gene polymorphisms were not significantly correlated to C0/D' of cyclosporine injection. In the final regression model, hemoglobin and CYP3A4*18B gene polymorphisms were significantly correlated to C0/D' of cyclosporine injection.Conclusion Cyclosporine injection can effectively improve the serum creatinine level in patients with subclinical or critical rejection; CYP3A4*18B gene polymorphism is significantly correlated to C0/D' of cyclosporine injection. |
| keywords:renal transplant cyclosporine injection gene polymorphisms CYP3A4 individualized medication |
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