ALRabeeah Danah, Almomen Aliyah, Alzoman Nourah, Arafah Maria
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.
Saudi Pharm J. 2023 Oct;31(10):101758. doi: 10.1016/j.jsps.2023.101758. Epub 2023 Aug 25.
Epilepsy is a common global neurological disorder. About 30% of epileptic patients are managed with anti-epileptic Drugs (AEDs). Since 2000, Levetiracetam (LEV) has been marketed around the world as an AED under the brand name Keppra, and recently more generics are found in the Saudi market as cheaper alternatives. The objective of this study is to evaluate the bioequivalence of LEV brand and generics available in the Saudi market in mice.
Pharmacokinetics (PK), liver function test, and behavioral studies were conducted for LEV brand and generic in different groups of Blab/c mice.
PK results show a significance difference in PK parameters mostly evidenced with generic 3, then generic 2. The only significant different between Keppra and generic 1 was in T. In addition, Keppra did not significantly increase liver enzymes in comparison to other generics. On the other hand, other generics showed less favorable results in increasing liver enzymes. Keppra reduced the number and intensity of epileptic attacks, had no mortality rate due to epilepsy, and was associated with less sever seizures attacks.
Keppra, the brand form of LEV, has better safety and efficacy profiles in mice compared to 3 generics found in the Saudi market. Therefore, we recommend evaluating the same parameters tested in this study in patients utilizing similar generics and brand to establish the existence of bioequivalence between LEV brand and generics.
癫痫是一种常见的全球性神经系统疾病。约30%的癫痫患者使用抗癫痫药物（AEDs）进行治疗。自2000年以来，左乙拉西坦（LEV）以品牌名开浦兰在全球上市作为一种抗癫痫药物，最近在沙特市场发现了更多的仿制药作为更便宜的替代品。本研究的目的是评估沙特市场上LEV品牌药和仿制药在小鼠体内的生物等效性。
对不同组的BALB/c小鼠进行了左乙拉西坦品牌药和仿制药的药代动力学（PK）、肝功能测试及行为学研究。
PK结果显示PK参数存在显著差异，主要体现在仿制药3上，其次是仿制药2。开浦兰与仿制药1之间唯一显著的差异在于达峰时间（T）。此外，与其他仿制药相比，开浦兰并未显著增加肝酶。另一方面，其他仿制药在增加肝酶方面显示出不太理想的结果。开浦兰减少了癫痫发作的次数和强度，没有因癫痫导致的死亡率，且与较轻的癫痫发作相关。
与在沙特市场发现的3种仿制药相比，左乙拉西坦的品牌药开浦兰在小鼠体内具有更好的安全性和有效性。因此，我们建议对使用类似仿制药和品牌药的患者评估本研究中测试的相同参数，以确定左乙拉西坦品牌药和仿制药之间生物等效性的存在。
