功能性G1199A ABCB1多态性可能对肾移植患者环孢素血药浓度有影响。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2013-08-01 Epub Date: 2013-05-30 DOI:10.1002/jcph.105

Gomaa Mostafa-Hedeab, Maha M Saber-Ayad, Inas A Latif, Sahier O Elkashab, Tarek H Elshaboney, Magdy Ibrahim Mostafa, Sanaa Abd El-Shafy, Magda M Zaki

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引用次数: 8

摘要

环孢素A (Cyclosporine A, CsA)的药代动力学表现出显著的个体间差异，这可能是由于编码p糖蛋白的ABCB-1基因多态性所致。本研究的目的是探讨ABCB-1基因多态性在肾移植患者移植后3个月内影响CsA血药浓度的作用。对接受CsA的肾移植患者(n = 40)进行ABCB -1 C3435T (I1145I)和G1199A (S400N)多态性基因分型。在移植后第7、30和90天测定CsA血药浓度。G1199A变体在稳定患者中显示出更高的CsA血药浓度，在第7天的低谷水平(198 vs. 136 ng/mL, P =。004, 196 vs. 125 ng/mL第30天，P =。007, 194 vs. 121 ng/mL，第90天，P =。005表示稳定组和不稳定组)。ABCB-1基因多态性对CsA血药浓度的影响较小。功能性G1199A多态性比非功能性C3435T更能影响药物水平。这种多态性可能在肾移植患者中具有潜在的预后价值。

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Functional G1199A ABCB1 polymorphism may have an effect on cyclosporine blood concentration in renal transplanted patients.

Cyclosporine A (CsA) shows significant inter-individual variability in its pharmacokinetics, which may be due to polymorphisms in ABCB-1 genes coding for P-glycoprotein. The aim of this study was to explore the role of genetic polymorphisms of ABCB-1 in affecting the CsA blood concentrations in renal transplanted patients over the first 3 months after transplantation. Renal transplanted patients receiving CsA (n = 40) were genotyped for ABCB -1 C3435T (I1145I) and G1199A (S400N) polymorphisms. CsA blood concentrations were measured on Day 7, 30, and 90 after transplantation. G1199A variant showed higher CsA blood concentrations in stable patients, that was significant for trough levels (198 vs. 136 ng/mL on Day 7, P = .004, 196 vs. 125 ng/mL on Day 30, P = .007, 194 vs. 121 ng/mL on Day 90, P = .005 for stable vs. unstable groups). Polymorphisms of ABCB-1 have only a minor effect on CsA blood concentrations. The functional G1199A polymorphism can affect the drug levels more than non-functional C3435T. This polymorphism might be of a potential prognostic value in renal transplanted patients.

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来源期刊

Journal of Clinical Pharmacology PHARMACOLOGY & PHARMACY-

自引率

3.40%

发文量

期刊介绍： The Journal of Clinical Pharmacology (JCP) is a Human Pharmacology journal designed to provide physicians, pharmacists, research scientists, regulatory scientists, drug developers and academic colleagues a forum to present research in all aspects of Clinical Pharmacology. This includes original research in pharmacokinetics, pharmacogenetics/pharmacogenomics, pharmacometrics, physiologic based pharmacokinetic modeling, drug interactions, therapeutic drug monitoring, regulatory sciences (including unique methods of data analysis), special population studies, drug development, pharmacovigilance, womens’ health, pediatric pharmacology, and pharmacodynamics. Additionally, JCP publishes review articles, commentaries and educational manuscripts. The Journal also serves as an instrument to disseminate Public Policy statements from the American College of Clinical Pharmacology.