Safety and pharmacokinetics of intravenous levetiracetam infusion as add-on in status epilepticus
Safety and pharmacokinetics of intravenous levetiracetam infusion as add-on in status epilepticus
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DOI：
10.1111/j.1528-1167.2008.01889.x
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发表时间：
2009-03-01
期刊：
影响因子：
5.6
通讯作者：
Vecht, Charles J.
中科院分区：
文献类型：
--
作者：
Uges, Joris W. F.;van Huizen, Marc D.;Vecht, Charles J.
目的：评价静脉注射左乙拉西坦（LEV）加用标准治疗方案治疗成人癫痫持续状态（SE）的可行性和安全性，并作为次要目的评估ivLEV在SE患者中的群体药代动力学（PK）模型。方法：在12名出现SE的成人中，尽快将2，500 mg ivLEV添加到标准化方案中，包括iv氯硝西泮和/或直肠地西泮，根据需要，随后是苯妥英或丙戊酸。ivLEV给药时间约为5分钟，一般在氯硝西泮给药后，无论是否需要进一步治疗。在24小时随访期间，观察患者的任何临床相关副作用。10例患者的PK分析血样可用。一个群体的PK模型，开发了迭代两阶段贝叶斯分析和健康volunteers.Results的PK数据进行比较：11例患者的中位年龄为60岁，包括在符合方案分析。5例被诊断为全身惊厥性SE，5例被诊断为部分惊厥性SE，1例被诊断为非惊厥性SE。从入院到ivLEV的中位时间为36分钟。没有严重的副作用可能与ivLEV的管理直接相关。在PK分析期间，4例患者显示出明确的分布相，其他患者缺乏。通过二室群体模型最好地描述了群体的PK。是说（标准差，SD）群体参数包括中央室分布容积：0.45（0.084）L/kg;全身清除率：0.0476（0.0147）L/h/kg;分布速率常数，中枢至外周室（k（12））：0.24（0.12）/h，外周至中枢（k（21））：0.70（0.22）/h。平均最大血药浓度为85（19）mg/L。讨论：在标准方案中加入ivLEV控制SE似乎是可行和安全的。ivLEV在SE患者中的PK数据与来自健康志愿者的早期值一致，证实了二室群体模型。
Purpose: To evaluate the feasibility and safety of intravenous (iv) levetiracetam (LEV) added to the standard therapeutic regimen in adults with status epilepticus (SE), and as secondary objective to assess a population pharmacokinetic (PK) model for ivLEV in patients with SE.Methods: In 12 adults presenting with SE, 2,500 mg ivLEV was added as soon as possible to standardized protocol, consisting of iv clonazepam and/or rectal diazepam, as needed followed by phenytoin or valproic acid. ivLEV was administered over approximately 5 min, in general after administration of clonazepam, regardless the need for further treatment. During 24-h follow-up, patients were observed for any clinically relevant side-effects. Blood samples for PK analysis were available in 10 patients. A population PK model was developed by iterative two-stage Bayesian analysis and compared to PK data of healthy volunteers.Results: Eleven patients with a median age of 60 years were included in the per protocol analysis. Five were diagnosed as generalized-convulsive SE, five as partial-convulsive SE, and one as a non-convulsive SE. The median time from hospital admission to ivLEV was 36 min. No serious side effects could be related directly to the administration of ivLEV. During PK analysis, four patients showed a clear distribution phase, lacking in the others. The PK of the population was best described by a two-compartment population model. Mean (standard deviation, SD) population parameters included volume of distribution of central compartment: 0.45 (0.084) L/kg; total body clearance: 0.0476 (0.0147) L/h/kg; distribution rate constants, central to peripheral compartment (k(12)): 0.24 (0.12)/h, and peripheral to central (k(21)): 0.70 (0.22)/h. Mean maximal plasma concentration was 85 (19) mg/L.Discussion: The addition of ivLEV to the standard regimen for controlling SE seems feasible and safe. PK data of ivLEV in patients with SE correspond to earlier values derived from healthy volunteers, confirming a two-compartment population model.