左乙拉西坦治疗小儿癫痫的影响分析

目的研究左乙拉西坦治疗小儿癫痫的疗效以及对智力的影响。方法在本院2017年4月-2019年5月收治的小儿癫痫患儿中选取74例开展研究,按照随机数表法分两组观察组和对照组,观察组37例,对照组37例,对照组采用奥卡西平进行治疗,观察组采用左乙拉西坦进行治疗,对比观察组与对照组组的治疗总有效率和智力评分变化。结果观察组与对照组比较,观察组的治疗总有效率较高,智力评分明显较高,两项对比差异有统计学意义(P <0.05)。结论左乙拉西坦治疗小儿癫痫有较好的治疗效果,治疗总有效率较高,且对患儿的智力有明显的改善作用,在实际临床小儿癫痫的治疗中具有较高的运用价值。     

RP-HPLC法同时测定人血浆中左乙拉西坦、奥卡西平及其活性代谢产物的浓度

目的：建立同时测定人血浆中左乙拉西坦、奥卡西平及其代谢产物单羟基卡马西平的含量测定方法,为左乙拉西坦与奥卡西平联合用药治疗癫痫提高临床疗效与用药安全性提供指导。方法：患者血浆样品经乙酸乙酯-二氯甲烷（70：30）沉淀蛋白处理后,以β-萘酚做内标,采用RP-HPLC法同时测定左乙拉西坦、奥卡西平及单羟基卡马西平的含量。色谱柱为Agilent C₁₈反相色谱柱,流动相为：乙腈（A）-水相（B）（由0.3%三氟乙酸与10 mmol·L^-1甲酸铵溶液按2：1体积比混合）梯度洗脱,流速1 mL·min^-1,柱温30℃,进样量10 μL,内标为β内萘酚,检测波长为210 nm （0~13 min）、225 nm （13~25 min）。结果：LEV、OXC、MHD血药浓度分别在2.0~60.0、2.0~60.0、3.0~96.0 μg·mL^-1范围内线性关系良好（r分别为LEV 0.999 7、MHD 0.999 6、OXC 0.999 8）,定量下限分别可达到2.0、2.0、3.0 μg·mL^-1;各组分的日内、日间精密度RSD均小于4%,各方法平均回收率均大于96%,LEV、OXC、MHD低、中、高3个浓度的提取回收率均>85%,稳定性的RSD均<15%。结论：该方法操作简便、快捷,专属性强,结果准确可靠,可用于左乙拉西坦、奥卡西平及其代谢产物单羟基卡马西平的临床血药浓度监测。     

左乙拉西坦缓释片在Beagle犬中的生物等效性研究

目的以Beagle犬为模型考察自制左乙拉西坦缓释片与参比缓释片(Keppra XR)在动物体内的生物等效性。方法 Beagle犬分别单剂量口服自制缓释片与参比制剂1 000mg,采用LC-MS/MS方法测定犬血浆中左乙拉西坦的浓度,通过药代动力学计算软件WinNonlin 5.2以非房室模型分别计算左乙拉西坦的药代动力学参数。结果自制缓释片与市售参比缓释片单剂量口服后,左乙拉西坦的达峰时间tmax分为1.67h和3.0h;峰浓度Cmax分别为89.50μg/ml和71.18μg/ml;消除半衰期t1/2分别为3.68h和3.50h;药时曲线下面积AUC(0-48)分别为826.57μg·h/ml和757.84μg·h/ml;药时曲线下面积AUC(0-∞)分别为826.68μg·h/ml和757.93μg·h/ml。与参比缓释片相比,自制左乙拉西坦缓释片的相对生物利用度为109.07%。结论初步判定两种制剂在犬体内具有类似的药代动力学特征和生物等效性。     

Hilar interneuron vulnerability distinguishes aged rats with memory impairment

Hippocampal interneuron populations are reportedly vulnerable to normal aging. The relationship between interneuron network integrity and age‐related memory impairment, however, has not been tested directly. That question was addressed in the present study using a well‐characterized model in which outbred, aged, male Long‐Evans rats exhibit a spectrum of individual differences in hippocampal‐dependent memory. Selected interneuron populations in the hippocampus were visualized for stereological quantification with a panel of immunocytochemical markers, including glutamic acid decarboxylase‐67 (GAD67), somatostatin, and neuropeptide Y. The overall pattern of results was that, although the numbers of GAD67‐ and somatostatin‐positive interneurons declined with age across multiple fields of the hippocampus, alterations specifically related to the cognitive outcome of aging were observed exclusively in the hilus of the dentate gyrus. Because the total number of NeuN‐immunoreactive hilar neurons was unaffected, the decline observed with other markers likely reflects a loss of target protein rather than neuron death. In support of that interpretation, treatment with the atypical antiepileptic levetiracetam at a low dose shown previously to improve behavioral performance fully restored hilar SOM expression in aged, memory‐impaired rats. Age‐related decreases in GAD67‐ and somatostatin‐immunoreactive neuron number beyond the hilus were regionally selective and spared the CA1 field of the hippocampus entirely. Together these findings confirm the vulnerability of hippocampal interneurons to normal aging and highlight that the integrity of a specific subpopulation in the hilus is coupled with age‐related memory impairment. J. Comp. Neurol. 521:3508‐3523, 2013. © 2013 Wiley Periodicals, Inc.     

维吾尔族、汉族癫痫患儿左乙拉西坦血药浓度与疗效及安全性的相关性研究

目的 研究新疆维吾尔族、汉族癫痫患儿左乙拉西坦（levetiracetam,LEV）血药浓度与临床疗效及安全性之间的相关性及差异性,同时预测可获得最佳疗效的LEV稳态谷浓度（steady valley concentration,Css）。方法 采用UPLC测定300例口服LEV的癫痫患儿的Css,分析族别对LEV Css的影响;观察其疗效和不良反应,并运用Logistic回归和受试者操作特征（receiver operating characteristic curve,ROC）曲线分析维吾尔族、汉族癫痫患儿血药浓度与疗效的关系。结果 LEV的浓度剂量比（concentration-dose ratio,CDR）结果显示其在维吾尔族、汉族患儿之间的差异均无统计学意义。2组患儿在0~4岁年龄组的CDR值差异有统计学意义（P<0.05）。2组患儿的LEV给药剂量和血药浓度均呈正相关,其中维吾尔族患儿组的相关性（r=0.628,P<0.01）优于汉族患儿组（r=0.545,P<0.01）。2组患儿LEV治疗有效率分别为78.43%,81.63%。2组患儿LEV治疗有效组与无效组的LEV Css差异均具有统计学意义（P<0.05）。Logistic回归分析发现在一定浓度范围（4.07~30.88 mg·L^-1）内,2组患儿LEV Css与疗效呈正相关。2组患儿中Css对于疗效的预判准确性均强于给药剂量。当维吾尔族患儿Css ≥ 13.15 mg·L^-1和汉族患儿Css ≥ 9.28 mg·L^-1时,其临床疗效均可得到更好的保证。结论 新疆维吾尔族、汉族癫痫患儿LEV血药浓度和临床疗效及安全性之间既存在相关性又存在不同程度的差异性,通过监测LEV Css可以提高临床疗效、避免不良反应,并为新疆癫痫患儿制订个体化给药方案提供参考。     

Effects of atorvastatin and aspirin on post-stroke epilepsy and usage of levetiracetam

Objective:Atorvastatin and aspirin have been used in treating different forms of epilepsy. However, their effect on post-stroke epilepsy (PSE) still needs to be validated by large-scale clinical studies. In addition, their impact on the use of the antiepileptic drug levetiracetam for post-stroke epilepsy remains to be explored. Thus, the aim of this study was to further evaluate the effect of atorvastatin and aspirin on PSE and their effect on the usage of the antiepileptic drug levetiracetam in PSE patients.Methods:Patients, aged 65 to 85 years, with newly diagnosed post-ischemic stroke epilepsy from August 30, 2014 to August 30, 2018 were included in the study, with the exclusion of those with coexisting conditions.Results:Initially, 1321 patients were included, and 780 remained in the study at the 1-year follow-up. During the study, atorvastatin treatment with or without aspirin reduced the number of clinical epileptic episodes in PSE patients. It also reduced the dosage of levetiracetam and achieved better control of epilepsy compared to levetiracetam mono-treatment. Aspirin co-treatment with levetiracetam did not result in a significant improvement. However, the combination of aspirin with atorvastatin significantly reduced the number of seizures compared to atorvastatin treatment alone.Conclusion:Atorvastatin and aspirin co-treatment with levetiracetam can reduce epilepsy in PSE patients and reduce the dosage of levetiracetam required for effective control of PSE.