ATP-binding castle protein G2 (ABCG2) is thought to inhibit the activities of certain gefitinib transporters, thereby affecting drug pharmacokinetics. The C421A polymorphism affects the function and expression of ABCG2 on the cell membrane. Previous studies have shown that proton-pump inhibitors (PPIs) inhibit gefitinib absorption, as well as the function of ABCG2. We evaluated the plasma concentrations of gefitinib in patients with and without the ABCG2 C421A polymorphism, who were or were not taking PPIs. In total, 61 patients with advanced epidermal-growth-factor-positive non-small-cell lung cancer were enrolled in this study. They were treated with gefitinib at a dose of 250 mg per day. Plasma gefitinib concentration and ABCG2 C421A status were determined after 2 weeks. The patients were divided into CC- and CA/AA genotype groups. We compared the trough and peak gefitinib levels and the area under the curve (AUC) values for 24-h gefitinib concentrations. We also compared these parameters among four groups distinguished according to the presence or absence of the polymorphism and PPI use. The mean trough gefitinib level and AUC value for 24-h gefitinib concentration were significantly lower in the CA/AA group compared to the CC group (mean trough level: 333.2 vs. 454.5 ng/mL, respectively, P = 0.021; AUC: 9949.9 vs. 13,085.4 ng・h/mL, respectively, P = 0.034). Among patients taking PPIs, the mean trough gefitinib level was significantly lower in the CA/AA group than the CC group (220.1 vs. 340.5 ng/mL, respectively, P = 0.033). The CA/AA-type of ABCG2 C421A polymorphism may be associated with lower gefitinib plasma concentrations.

ATP 结合城堡蛋白 G2 (ABCG2) 被认为可以抑制某些吉非替尼转运蛋白的活性，从而影响药物的药代动力学。C421A多态性影响ABCG2在细胞膜上的功能和表达。先前的研究表明，质子泵抑制剂 (PPI) 会抑制吉非替尼的吸收以及 ABCG2 的功能。我们评估了有和没有 ABCG2 C421A 多态性、服用或未服用 PPI 的患者的吉非替尼血浆浓度。总共有 61 名晚期表皮生长因子阳性非小细胞肺癌患者参加了这项研究。他们接受了每天 250 毫克剂量的吉非替尼治疗。2 周后确定血浆吉非替尼浓度和 ABCG2 C421A 状态。患者分为CC-和CA/AA基因型组。我们比较了 24 小时吉非替尼浓度的谷值和峰值以及曲线下面积 (AUC) 值。我们还在根据多态性和 PPI 使用的存在与否区分的四组中比较了这些参数。与 CC 组相比，CA/AA 组的吉非替尼平均谷水平和 24 小时吉非替尼浓度的 AUC 值显着降低（平均谷水平：分别为 333.2 和 454.5 ng/mL，P  = 0.021；AUC：分别为 9949.9 和 13,085.4 ng·h/mL，P  = 0.034)。在服用 PPI 的患者中，CA/AA 组的平均吉非替尼谷水平显着低于 CC 组（分别为 220.1 和 340.5 ng/mL，P  = 0.033）。ABCG2 C421A 多态性的 CA/AA 型可能与较低的吉非替尼血浆浓度有关。