College of Medicine, Beni-Suif University, Beni-Suif, Egypt.
J Clin Pharmacol. 2013 Aug;53(8):827-33. doi: 10.1002/jcph.105. Epub 2013 May 30.
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.
环孢素 A（CsA）在药代动力学方面表现出显著的个体间变异性，这可能是由于编码 P-糖蛋白的 ABCB-1 基因的多态性所致。本研究旨在探讨 ABCB-1 基因多态性对肾移植患者移植后 3 个月内 CsA 血药浓度的影响。对接受 CsA 治疗的肾移植患者（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 天测量 CsA 血药浓度。在稳定患者中，G1199A 变异型显示出更高的 CsA 血药浓度，在谷值水平上差异具有统计学意义（第 7 天分别为 198 vs. 136ng/mL，P=0.004，第 30 天分别为 196 vs. 125ng/mL，P=0.007，第 90 天分别为 194 vs. 121ng/mL，P=0.005，稳定组与不稳定组比较）。ABCB-1 多态性对 CsA 血药浓度的影响较小。功能性 G1199A 多态性可能比非功能性 C3435T 多态性对药物水平的影响更大。这种多态性可能对肾移植患者具有潜在的预后价值。
