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成年癫痫患者中拉科酰胺血清浓度的种族差异。

Racial variations in lacosamide serum concentrations in adult patients with epilepsy.

作者信息

Zutshi Deepti, Yarraguntla Kalyan, Mahulikar Advait, Seraji-Bozorgzad Navid, Shah Aashit K, Basha Maysaa M

机构信息

Comprehensive Epilepsy Center, Wayne State University/Detroit Medical Center, Detroit, MI, USA.

Department of Neurology, University of Michigan, Ann Arbor, Detroit, MI, USA.

出版信息

J Neurol Sci. 2020 May 15;412:116742. doi: 10.1016/j.jns.2020.116742. Epub 2020 Feb 19.

Abstract

Lacosamide (LCM) is a third-generation anti-epileptic drug (AED) for partial-onset epilepsy with minimal hepatic metabolism and drug-drug interactions. The impact of individual patient variables such as race on drug metabolism have been under-reported in AEDs and LCM has not been specifically investigated. Our aim was to assess the role race plays on serum LCM levels in the management of epilepsy. Thus, we retrospectively reviewed patients with focal seizures who received LCM and had LCM levels as part of their routine clinical care in our Level IV Epilepsy Center. Variables including age, race, gender, LCM serum levels, LCM daily dose, and concomitant AEDs were collected and analyzed. A total of 93 patients with 1-3 clinic visits yielded 122 LCM serum levels. African Americans (AA) comprised 62.3% of our serum samples. Daily LCM doses averaged 350 mg/day (range 50-1000 mg/day). Eighty-nine percent of patients took 1-2 other AEDs. Overall, AA patients had lower LCM levels (mean 6.8 μg/mL) compared to White patients (mean of 7.1 μg/mL) (p = .017) even when considering for the daily dose effect (p = .007). Analysis of co-variables did not have significant effect on LCM levels. Overall, AA patients had a weaker relationship between LCM daily dose (adjusted for weight) and serum levels as compared to White patients and require a higher LCM dose per weight to achieve similar levels. Differences in pharmacogenetics may play an important role in these findings and focus on how these variations impact seizure burden.

摘要

拉科酰胺(LCM)是一种用于部分性发作癫痫的第三代抗癫痫药物(AED),其肝脏代谢和药物相互作用极小。个体患者变量(如种族)对药物代谢的影响在抗癫痫药物中报道较少,且拉科酰胺尚未进行专门研究。我们的目的是评估种族在癫痫治疗中对血清拉科酰胺水平的作用。因此,我们回顾性分析了在我们的四级癫痫中心接受拉科酰胺治疗且其拉科酰胺水平作为常规临床护理一部分的局灶性发作患者。收集并分析了包括年龄、种族、性别、拉科酰胺血清水平、拉科酰胺每日剂量和联合使用的抗癫痫药物等变量。共有93例患者进行了1 - 3次门诊就诊,共获得122个拉科酰胺血清水平数据。非裔美国人(AA)占我们血清样本的62.3%。拉科酰胺每日平均剂量为350毫克/天(范围为50 - 1000毫克/天)。89%的患者服用1 - 2种其他抗癫痫药物。总体而言,即使考虑每日剂量效应(p = 0.007),非裔美国患者的拉科酰胺水平(平均6.8μg/mL)仍低于白人患者(平均7.1μg/mL)(p = 0.017)。协变量分析对拉科酰胺水平没有显著影响。总体而言,与白人患者相比,非裔美国患者拉科酰胺每日剂量(根据体重调整)与血清水平之间的关系较弱,且每单位体重需要更高的拉科酰胺剂量才能达到相似水平。药物遗传学差异可能在这些结果中起重要作用,并关注这些差异如何影响癫痫发作负担。

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