Department of Laboratory Diagnostics, University Hospital Centre Zagreb , Zagreb, Croatia.
Ther Drug Monit. 2012 Oct;34(5):518-25. doi: 10.1097/FTD.0b013e31826517c6.
Epilepsy is treated with a variety of anticonvulsants that are often used concomitantly. Therefore, therapeutic drug monitoring is often necessary. Along with clinical and environmental factors, genetic predisposition has been recognized to be relevant for interindividual variability in drug response. Polymorphic transporter proteins such as P-glycoprotein significantly influence pharmacokinetics and bioavailability of many structurally unrelated drugs. The aim of the study was to evaluate the impact of polymorphisms in the P-glycoprotein-encoding gene ABCB1 (C1236T, G2677T/A, C3435T) on antiepileptic drug disposition.
We recruited 222 patients with epilepsy who were prescribed lamotrigine in monotherapy or polytherapy. Lamotrigine plasma concentrations were analyzed and compared with ABCB1 gene variants. The ABCB1 genotyping was performed by real-time polymerase chain reaction methods. The therapeutic drug monitoring was performed by high-performance liquid chromatography-diode array detector (DAD) and immunoassay.
A significant correlation was confirmed between lamotrigine concentration and additional drugs (P < 0.001). In the whole group, statistical analysis showed correlations between lamotrigine concentrations and ABCB1 C1236T variants: 10.1 and 6.5 μmol/L for CC versus CT + TT, respectively (P = 0.021), and for dose corrected lamotrigine 0.068 and 0.053 μmol·L·mg, for CC versus CT + TT, respectively (P = 0.017). Analysis of a specific haplotype showed that 1236C-2677G-3435C carriers had higher lamotrigine concentrations than 1236T-2677G-3435T carriers (P < 0.001), followed by 1236T-2677T-3435C carriers (P < 0.001).
ABCB1 C1236T, G2677T/A, C3435T polymorphisms have an influence on lamotrigine serum concentrations.
癫痫的治疗方法有很多种，其中包括联合使用多种抗癫痫药物。因此，通常需要进行治疗药物监测。除了临床和环境因素外，遗传易感性也与药物反应的个体间差异有关。多态性转运蛋白如 P 糖蛋白显著影响许多结构上无关的药物的药代动力学和生物利用度。本研究旨在评估 P 糖蛋白编码基因 ABCB1（C1236T、G2677T/A、C3435T）多态性对抗癫痫药物处置的影响。
我们招募了 222 名接受拉莫三嗪单药或联合治疗的癫痫患者。分析并比较了拉莫三嗪的血浆浓度与 ABCB1 基因变异。采用实时聚合酶链反应方法进行 ABCB1 基因分型。采用高效液相色谱-二极管阵列检测器（DAD）和免疫测定法进行治疗药物监测。
我们证实拉莫三嗪浓度与附加药物之间存在显著相关性（P<0.001）。在整个组中，统计分析显示拉莫三嗪浓度与 ABCB1 C1236T 变异之间存在相关性：CC 与 CT+TT 相比分别为 10.1 和 6.5 μmol/L（P=0.021），而对于剂量校正的拉莫三嗪，CC 与 CT+TT 相比分别为 0.068 和 0.053 μmol·L·mg（P=0.017）。对特定单倍型的分析表明，1236C-2677G-3435C 携带者的拉莫三嗪浓度高于 1236T-2677G-3435T 携带者（P<0.001），其次是 1236T-2677T-3435C 携带者（P<0.001）。
ABCB1 C1236T、G2677T/A、C3435T 多态性对拉莫三嗪的血清浓度有影响。
