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levetiracetam induces tyrosine kinase receptor B expression in SH-SY5Y cells

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Neural Regeneration Research 2011年第14期6卷 1082-1085页

作者： Danrong Lei Shengfu Li Xiaoyi Zou Department of Neurology West China Hospital Sichuan University Chengdu 610041 Sichuan Province China Laboratory of Transplantation Immunity Sichuan University Chengdu 610041 Sichuan Province China

Tyrosine kinase receptor B （TrkB） plays an important role in long-term potentiation and memory *** present study used all-trans retinoic acid to induce TrkB expression in SH-SY5Y cells,and observed the effects of levetiracetam （LEV） on TrkB *** exposure to 10,50,and 100 μg/mL LEV,the number of TrkB-positive cells,and average absorbance value were *** demonstrated that LEV can induce TrkB expression in SH-SY5Y cells.

关键词： levetiracetam tyrosine kinase receptor B brain-derived neurotrophic factor cognition SH-SY5Y cells neural regeneration

levetiracetam administration is correlated with lower mortality in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes: a retrospective study

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Chinese Medical Journal 2019年第3期132卷 269-274页

作者： Zhe Zhang Dan-Hua Zhao Xu-Tong Zhao Xiao Zhang Hui Xiong Xin-Hua Bao Yun Yuan Zhao-Xia Wang Department of Neurology Peking University First HospitalBeijing 100034China Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China Department of Neurology Peking University International HospitalBeijing 102206China Department of Neurology Beijing Friendship HospitalCapital Medical UniversityBeijing 100050China Department of Pediatrics Peking University First HospitalBeijing 100034China

Background:Studies on the relationship between antiepileptic drug (AED) administration and clinical outcomes in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) remain scarce. levetiracetam (LEV) is an AED that is neuroprotective in various neurologic disorders. This study aimed to determine the impact of LEV on the outcome of ***:A retrospective, single-center study was performed based on a large cohort of patients with MELAS with a history of seizures (n=102). Decisions on antiepileptic therapies were made empirically. Patients were followed up for 1 to 8 years (median, 4 years) and divided into 2 groups based on whether LEV was administered (LEV or non-LEV). The modified Rankin scale (mRS) scores and mortality risks were analyzed in all ***:LEV, carbamazepine, benzodiazepines, topiramate, oxcarbazepine, valproate, and lamotrigine were administered in 48, 37, 18, 13, 11, 9, and 9 patients, singly or in combination, respectively. The mean mRS score of the LEV group (n=48) was lower than that of the non-LEV group (n=54;mean±standard deviation, 2.79±1.47 vs. 3.83±1.93, P=0.006) up to the end of the study. Nevertheless, there was no difference in the proportion of subjects without disability (mRS ranging 0-1) between the groups (P=0.37). The multivariate regressions revealed that LEV treatment was associated with lower mRS scores (odds ratio 0.32, 95% confidence interval [CI] 0.15-0.68, P=0.003) and mortality rates (hazard ratio 0.24, 95% CI 0.08-0.74, P=0.013). There was a significant difference in the Kaplan-Meier survival curves between the groups (χ^2=4.29, P=0.04).Conclusions:The LEV administration is associated with lower mortality in patients with MELAS in this retrospective study. Further laboratory research and prospective cohort studies are needed to confirm whether LEV has neuroprotective effects on patients with mitochondrial diseases.

关键词： Syndrome Seizures Epilepsy Anticonvulsants levetiracetam Survival analysis

Effect of levetiracetam and valproate on late‑onset post‑traumatic seizures

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Acta Epileptologica 2023年第2期6卷 86-89页

作者： Yanli Wang Yiqi Wang Huifang Wang Xiaoping Du Jie Miao James X.Tao Meizhen Sun Department of Rehabilitation Shanxi Traditional Chinese Medical HospitalTaiyuan 030012China Department of Neurology The First Hospital of Shanxi Medical UniversityTaiyuan 030012China Department of Neurology University of ChicagoChicagoIL 60601USA

Background To compare the preventive effects of levetiracetam and valproate on late-onset post-traumatic seizures in patients with traumatic brain injury(TBI).Methods A total of 95 patients with TBI were recruited from 2017 to *** were randomized into three groups:levetiracetam(LEV)group(n=30)receiving LEV treatment(500 mg,bid,po);valproate group(n=32)receiving sodium valproate(500 mg/d,once daily,po);and control group(n=33)receiving no anti-seizure *** and valproate were given to corresponding groups within seven days after TBI,and the administration lasted for one *** incidence of epilepsy and adverse events were evaluated at 7 days and 12 months *** The cumulative incidences of late post-traumatic seizures at the 12-month follow-up in the LEV,valproate,and control groups were 3.33%,12.50%and 15.63%,*** cumulative incidence of late post-traumatic seizures in the LEV group was significantly lower than those in the valproate and control groups(P0.05).Conclusions LEV can reduce the cumulative incidence of late post-traumatic seizures,whereas valproate can not.

关键词： levetiracetam Valproate Post-traumatic seizure

levetiracetam-Associated Acute Kidney Injury and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome

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Open Journal of Nephrology 2014年第4期4卷 152-155页

作者： Mathieu Leblanc Martin Plaisance Internal Medecine Residency Program Faculté de Médecine et des Sciences de la santé Université de Sherbrooke Sherbrooke Canada Nephrology Division Department of Medicine Centre Hospitalier Universitaire de Sherbrooke Sherbrooke Canada

DRESS syndrome is a severe drug induced reaction. Acute kidney injury (AKI) is sometimes present in the form of an acute interstitial nephritis. We present the case of a 75-year-old man with glioblastoma who developed a DRESS two months after starting levetiracetam and a few days after stopping dexamethasone. His skin and kidneys improved after removing levetiracetam and introducing again corticosteroids. DRESS has been reported more frequently with other antiepileptics, rarely with levetiracetam. Clinicians should add this drug to the list of potential causes of AKI.

关键词： Acute Kidney Injury DRESS Syndrome HSV-1 levetiracetam

Antimyoclonic Effect of levetiracetam and Clonazepam Combined Treatment on Myoclonic Epilepsy with Ragged-Red Fiber Syndrome with m.8344A〉G Mutation

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Chinese Medical Journal 2018年第20期131卷 2433-2438页

作者： Li-Jun Su Yu-Liang Wang Tao Han Shan Qiao Ke-Jun Zang Huai-Kuan Wu Yong-Xin Su Ling-Ling Liu Xue-Wu Liu Department of Neurology Qilu Hospital of Shandong University Jinan Shandong 251102 China Department of Neurology Binzhou Medical University Hospital Binzhou Shandong 256603 China Department of Neurology Xuanwu Hospital Capital Medical University Beijing 100053 China Department of Neurology Qianfoshan Hospital of Shandong Province Jinan Shandong 250014 China

Background： Treatment of myoclonic seizures in myoclonic epilepsy with ragged-red fibers （MERRFs） has been empirical and ineffective. Guideline on this disease is not available. Additional trials must be conducted to find more suitable treatments for it. In this study, the antimyoclonic effects ofmonotherapies, including levetiracetam （LEV）, clonazepam （CZP）, valproic acid （VPA）, and topiramate （TPM） compared to combination therapy group with LEV and CZP on MERRF, were evaluated to find a more advantageous approach on the treatment of myoclonic seizures. Methods： Treatments of myoclonic seizures with VPA, LEV, CZP, and TPM were reported as monotherapies in 17 MERRF patients from Qilu Hospital between 2003 and 2016, who were diagnosed through clinical data and genetic testing. After 1-4 months oflbllow-up （mean： 82.9 ± 28.1 days）, 12 patients that exhibited poor responses to monotherapy were given a combined treatment consisting of LEV and CZP subsequently. The lbllow-up period was 4-144 months （mean： 66.3 ± 45.3 months）, the effective rates of monotherapy group （17 patients） and combination therapy group （12 patients） were analyzed by Chi-square test. Results： The m.8344 A〉G mutation was detected in all patients. There were lbur patients with partial response （4/17, two in the CZP group and two in the LEV group）, ten patients with stable disease （10/17, six in the CZP group, three in the LEV group, and one in the TPM group）, and three patients with progressive disease （3/18, two in the VPA group and one in the TPM group）. Twelve of the patients with LEV combined with CZP showed a positive effect and good tolerance （12/12）, eight of them demonstrated improved cognition and coordination. There was a significant difference between the monotherapy group and combination therapy gToup in the efficacy ofantimyoclonic seizures （χ^2 = 13.7, P 〈 0.001 ）. Conclusions： LEV in combination with CZP is an efficient and sale treatment for myoclonic seizures in patients with this di

关键词： Clonazepam levetiracetam Myoclonic Epilepsy with Ragged-Red Fibers Myoclonic Seizures

levetiracetam的合成及其制剂研究

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Levetiracetam的合成及其制剂研究

作者：张烨辽宁大学

学位级别：硕士

levetiracetam化学名称为(S)-α-乙基-2-氧代-1-吡咯烷乙酰胺,为吡咯烷酮类新型抗癫痫药物,是一种广谱可有效控制癫痫发作的第二代乙酰胆碱激动剂。因其具有独特的抗癫痫作用机制和显著的药动学特点,治疗指数高、安全性好、不良反应少,... 详细信息

levetiracetam化学名称为(S)-α-乙基-2-氧代-1-吡咯烷乙酰胺,为吡咯烷酮类新型抗癫痫药物,是一种广谱可有效控制癫痫发作的第二代乙酰胆碱激动剂。因其具有独特的抗癫痫作用机制和显著的药动学特点,治疗指数高、安全性好、不良反应少,逐渐受到了医生和病人的青睐。levetiracetam不仅仅可以作为癫痫的单药治疗,还可以用于儿童癫痫和全身性癫痫的治疗,在癫痫治疗领域显示出了广泛的应用前景,但因其原研药Keppra价格较高,使levetiracetam在我国的癫痫病人的治疗上受到了限制。为此,本文对levetiracetam的合成路线进行了深入研究,并进行了相关的制剂研究,按照规范进行了结构确证、质量研究等工作内容,以期从根本上降低成本,使更多的癫痫病人受益。在研究分析文献的基础上,通过优化工艺,确定以(S)-2-氨基丁酰胺酒石酸盐为原料,在异丙醇中滴加氢氧化钾的异丙醇溶液游离得到(S)-2-氨基丁酰胺,再与氯化氢的异丙醇溶液作用得到(S)-2-氨基丁酰胺盐酸盐,通过与4-氯丁酰氯酰化、关环得到levetiracetam粗品,经乙酸乙酯/丙酮混合溶剂精制得到levetiracetam,最终收率为：58.5-67.2%。通过紫外吸收光谱、红外吸收光谱、质谱、核磁共振氢谱等手段,证明样品与levetiracetam的结构一致。该合成工艺路线反应条件比较温和,原料药易得,操作简便,生产成本降低,比较适合于工业化生产。由于目前各国药典都没有将levetiracetam收录,因此暂时没有可以依据的法定质量标准。本文根据我国2010版药典的要求,应用现代药物分离分析技术,对levetiracetam进行分析方法、质量评价以及稳定性考察等方面的研究,包括性状、比旋度、鉴别、杂质检查、含量测定等方面,建立了测定levetiracetam、 levetiracetam右消旋体以及有关杂质的HPLC方法,根据以上结果初步制定了本品的质量标准。研制了levetiracetam片剂和注射液,并对其进行了质量研究。根据优时比制药公司(UCB)公司专利,相关文献和2010药典的规定对处方进行了初步的研究和考察,所制备的制剂符合规定。

关键词： levetiracetam 合成工艺质量研究片剂注射剂

Beneficiality of combined levetiracetam, clonazepam for myoclonus in MERRF requires further confirmation

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Chinese Medical Journal 2019年第5期132卷 622-623页

作者： Josef Finsterer Department of Neurology City Hospital Rudolfstiftung Messerli Institute Veterinary University of Vienna Vienna 1180 Austria

To the Editor: With interest, we read the article by Su et al[1] about the antiepileptic drug (AED) treatment of 17 patients with genetically confirmed myoclonic epilepsy with ragged-red fibers (MERRF) syndrome. It wa... 详细信息

关键词： combined levetiracetam myoclonus MERRF

Pharmacokinetics, safety and bioequivalence of intravenous and oral formulations of the antiepileptic drug levetiracetam in healthy Chinese volunteers

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Journal of Chinese Pharmaceutical Sciences 2018年第11期27卷 777-786页

作者： Lanlan Hu Juan Zhou Huan Zou Yue Zhang Jianlin Tang Base for Drug Clinical Trial Xinqiao Hospitalthe Third Military Medical UniversityChongqing 400037China

The intravenous formulation of levetiracetam (LEV)has been available in clinical practice worldwide for several years,but not in *** the present study,we aimed to evaluate the bioequivalence of intravenous and oral LEV (tablet), an antiepileptic drug,in healthy Chinese *** randomized,single-dose (1500mg),open-label,2-period crossover trials were conducted as follows:study A,15-min infusion;study B,45-min infusion.A total of 22healthy men participated in study A,and 24healthy men and woman were enrolled in study *** study A,blood samples were collected after termination of each *** study B,samples were collected after oral or after the start of the intravenous *** and the ratio of intravenous/oral LEV for AUC 0-t and Cmax were *** 90% confidence intervals of Cmax and AUC0-t ratios for LEV 1500-mg tablets versus 15-min intravenous administration were outside the bioequivalence limits (80.00%-125.00%). For LEV 45-min intravenous administration,bioequivalence versus 1500-mg tablets was within the range for Cmax and AUC 0-t. The most frequently adverse event (AE)was somnolence.A total of eight subjects experienced nine mild AEs in study A, and 19subjects experienced 29mild AEs in study *** infusions (15 and 45 min)of 1500-mg LEV were as well tolerated as the oral *** was demonstrated by 45-min ***,direct conversion from oral to intravenous LEV 1500 mg (45-min infusion),or vice versa,was possible.

关键词： levetiracetam Epilepsy Intravenous formulation Bioequivalence Safety and tolerability

Acute Kidney Injury with levetiracetam in Patient with Epilepsy: A Case Report

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Case Reports in Clinical Medicine 2022年第3期11卷 48-54页

作者： Khalid Al-Quliti Rakan Maher Alhujeily Neurology Division Department of Medicine College of Medicine Taibah University Al-Madinah Almunwwarah Saudi Arabia College of Medicine Taibah University Al-Madinah Almunwwarah Saudi Arabia

Epilepsy is a common neurological disorder in neurology clinic. levetiracetam is considered as one of common antiepileptic drugs used to manage epilepsy with good efficacy and tolerability profile. It is renally excreted and not depending on the cytochrome p450. It has adverse effects reported as somnolence, headaches, dizziness, depression and anxiety. Also, it was reported that levetiracetam can cause Acute kidney injury (AKI), renal profile disturbance, that may be related to its way of excretion and possible nephrotoxicity especially with high loading dose. We are reporting a young female patient with epilepsy presented to hospital with status epileptcus and started on loading dose of levetiracetam 3 grams and then maintenance dose of 1 gram twice daily seizure were controlled but she developed acute kidney injury that improved after discontinue leveriracetam and medical management without renal dialysis and discharged home in stable condition. Physician and health care providers should be aware of such rare adverse reaction and available management options for better patient care and outcome.

关键词： Acute Kidney Injury Epilepsy levetiracetam