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<p><b>Background and Objectives</b> The steady-state disposition lamotrigine (LTG) varies widely among patients with epilepsy, especially in the presence of concomitant antiseizure drugs. In this study, we investigate the potential role of transporter gene polymorphisms in <i>ABCC1</i>, <i>ABCC2</i>, <i>ABCG2</i>,<i> SLCO1A2</i> and <i>SLCO1B1</i> on the steady-state disposition of LTG and on the lamotrigine-valproate (LTG-VPA) interaction, and their effect on the therapeutic efficacy in adults with epilepsy.</p><p><b>Methods</b> Adults with epilepsy on LTG monotherapy or LTG-VPA treatment were genotyped and steady-state LTG and VPA morning troughs were determined. The number of seizures within a one-year follow-up period was used to evaluate the antiepileptic efficacy.</p><p><b>Results</b> A total of 331 patients with epilepsy were enrolled, including 267 receiving LTG monotherapy and 64 receiving LTG combined with VPA. Steady-state LTG plasma troughs and normalized troughs were significantly higher in the LTG-VPA group than in the LTG monotherapy group (8.82 vs. 4.43&#xa0;µg/mL, <i>p</i> &lt; 0.001; 4.12 vs. 1.51&#xa0;µg/mL, <i>p</i> &lt; 0.001). Among the investigated transporter gene polymorphisms, only <i>SLCO1B1</i> rs4149032 showed a significant association with LTG concentrations in monotherapy. Overall, 77.8% (242/331) of patients achieved a therapeutic response, with a markedly higher response rate in the LTG-VPA group compared with LTG alone (92.1% vs. 76.5%, <i>p</i> = 0.0009). Multivariate logistic regression identified LTG plasma concentration and sex as independent predictors of favorable seizure control.</p><p><b>Conclusions</b> The polymorphisms of <i>SLCO1B1</i> rs4149032 may affect LTG plasma troughs in patients with LTG monotherapy. LTG plasma concentrations are a major determinant of antiepileptic therapeutic efficacy with or without VPA co-therapy, with higher exposure associated with improved seizure control.</p>

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Effect of transporter gene polymorphisms and valproate co-medication on the steady-state disposition of lamotrigine and their effect on efficacy in adults with epilepsy

  • 期刊论文

  • 发表日期：

    2026年3月6日

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  • Changsong Wu,
  • Rui He,
  • Jianghuan Zheng,
  • Jing Yang,
  • Yanling Pan,
  • Ruyu Tao,
  • Xue Lan,
  • Jinxingyi Wang

摘要

Background and Objectives The steady-state disposition lamotrigine (LTG) varies widely among patients with epilepsy, especially in the presence of concomitant antiseizure drugs. In this study, we investigate the potential role of transporter gene polymorphisms in ABCC1, ABCC2, ABCG2, SLCO1A2 and SLCO1B1 on the steady-state disposition of LTG and on the lamotrigine-valproate (LTG-VPA) interaction, and their effect on the therapeutic efficacy in adults with epilepsy.

Methods Adults with epilepsy on LTG monotherapy or LTG-VPA treatment were genotyped and steady-state LTG and VPA morning troughs were determined. The number of seizures within a one-year follow-up period was used to evaluate the antiepileptic efficacy.

Results A total of 331 patients with epilepsy were enrolled, including 267 receiving LTG monotherapy and 64 receiving LTG combined with VPA. Steady-state LTG plasma troughs and normalized troughs were significantly higher in the LTG-VPA group than in the LTG monotherapy group (8.82 vs. 4.43 µg/mL, p < 0.001; 4.12 vs. 1.51 µg/mL, p < 0.001). Among the investigated transporter gene polymorphisms, only SLCO1B1 rs4149032 showed a significant association with LTG concentrations in monotherapy. Overall, 77.8% (242/331) of patients achieved a therapeutic response, with a markedly higher response rate in the LTG-VPA group compared with LTG alone (92.1% vs. 76.5%, p = 0.0009). Multivariate logistic regression identified LTG plasma concentration and sex as independent predictors of favorable seizure control.

Conclusions The polymorphisms of SLCO1B1 rs4149032 may affect LTG plasma troughs in patients with LTG monotherapy. LTG plasma concentrations are a major determinant of antiepileptic therapeutic efficacy with or without VPA co-therapy, with higher exposure associated with improved seizure control.