Alotaibi Haya, Alenazi Sarah Sulaiman, Alrubia Sarah, Arafah Maria, Alzoman Nourah, Almomen Aliyah
Department of Pharmaceutical, Chemistry College of Pharmacy, King Saud University, Riyadh, 11495, Saudi Arabia.
Department of Pathology College of Medicine, King Saud University, Riyadh, 11495, Saudi Arabia.
BMC Pharmacol Toxicol. 2025 Jul 1;26(1):125. doi: 10.1186/s40360-025-00963-7.
Epilepsy is one of the most chronic neurological disorders worldwide. In 2023, the World Health Organization (WHO) estimates that approximately 50 million individuals globally would be affected by epilepsy. Furthermore, it was suggested that as many as 70% of patients could experience a life without seizure if they received appropriate treatment. Lamotrigine (LTG) is one of the newer antiepileptic drugs. It has been globally marketed under the name Lamictal. Due to the increasing demand for transformation between brand and generic products, this study aims to evaluate the product safety and efficacy on liver enzymes, as well as the behavioral effects and pharmacokinetics of lamotrigine, specifically the brand Lamictal and its generics available in the Saudi market.
Male albino mice with an average weight of 24 g will be randomly divided into groups (n = 6) for pharmacokinetic study, liver enzyme analysis, and behavioral evaluation of brand Lamictal and generics. One-way ANOVA and Bonferroni's post hoc test will be used to compare results in the different animal groups. Statistical significance p-values will be determined at P < 0.05.
The study found that generics had a significant difference PK parameters were compared to those of Lamictal, which was mostly found in generics 1 and 2. Liver analysis revealed liver enzyme elevation in all generics compared to the brand Lamictal, which was primarily pronounced in AST and GGT with generic 2, and an increase in ALT, ALP, and GGT was primarily found in generic 1. The behavioral study indicates higher seizure attacks in generics compared to the brand Lamictal, with an increase in mortality rates mainly observed with generics 1 and 2.
This research finds that there is a significant difference in safety and efficacy between brand and generic lamotrigine products in terms of liver enzyme tests, behavioral analysis, and PK parameters. Future studies to evaluate lamotrigine brand and generic drugs in humans are recommended.
癫痫是全球最常见的慢性神经系统疾病之一。2023年，世界卫生组织（WHO）估计，全球约有5000万人受癫痫影响。此外，有人指出，如果接受适当治疗，多达70%的患者可以过上无癫痫发作的生活。拉莫三嗪（LTG）是较新的抗癫痫药物之一。它已在全球以拉莫三嗪（Lamictal）的名称销售。由于品牌产品和仿制药之间转换的需求不断增加，本研究旨在评估拉莫三嗪对肝酶的产品安全性和有效性，以及其行为效应和药代动力学，特别是沙特市场上的品牌拉莫三嗪及其仿制药。
平均体重24克的雄性白化小鼠将被随机分为几组（n = 6），用于品牌拉莫三嗪及其仿制药的药代动力学研究、肝酶分析和行为评估。单向方差分析和Bonferroni事后检验将用于比较不同动物组的结果。统计学显著性p值将在P < 0.05时确定。
研究发现，仿制药与拉莫三嗪相比，药代动力学参数有显著差异，这在仿制药1和仿制药2中最为常见。肝脏分析显示，与品牌拉莫三嗪相比，所有仿制药的肝酶均升高，其中仿制药2的天冬氨酸转氨酶（AST）和γ-谷氨酰转移酶（GGT）升高最为明显，仿制药1中谷丙转氨酶（ALT）、碱性磷酸酶（ALP）和GGT升高最为明显。行为学研究表明，与品牌拉莫三嗪相比，仿制药的癫痫发作次数更多，死亡率增加主要见于仿制药1和仿制药2。
本研究发现，在肝酶测试、行为分析和药代动力学参数方面，品牌拉莫三嗪和仿制药在安全性和有效性上存在显著差异。建议未来开展评估拉莫三嗪品牌药和仿制药在人体中的研究。
