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连续静脉-静脉血液滤过治疗的危重症患者的拉考酰胺药代动力学。

Lacosamide Pharmacokinetics in a Critically Ill Patient Receiving Continuous Venovenous Hemofiltration.

机构信息

Department of Pharmacy, University of Maryland Medical Center, Baltimore, Maryland.

University of Maryland School of Pharmacy, Baltimore, Maryland.

出版信息

Pharmacotherapy. 2018 Feb;38(2):e17-e21. doi: 10.1002/phar.2063. Epub 2017 Dec 18.

Abstract

Lacosamide is a new-generation antiepileptic drug (AED) that is eliminated by both hepatic and renal mechanisms. Lacosamide elimination by continuous renal replacement therapy (CRRT) has never been studied. The objective of this case report was to describe lacosamide pharmacokinetics in the setting of CRRT. We describe a single patient admitted to the study center with status epilepticus and multiorgan failure. The patient required both continuous venovenous hemofiltration (CVVH) and several AEDs. He was receiving intravenous lacosamide 200 mg twice/day at steady state prior to sampling. Plasma lacosamide concentrations were derived using a validated high-performance liquid chromatography method. Parameters were calculated using Phoenix WinNonlin 7.1 software. The peak concentration at steady state was 7.7 mg/L, the trough concentration was 5.9 mg/L (goal 5-12 mg/L). The volume of distribution was 0.7 L/kg, the elimination half-life was 21 hours, and the sieving coefficient was 0.8 (± 0.06). Lacosamide was cleared by CVVH as demonstrated by the sieving coefficient, but plasma concentrations remained within goal range throughout the dosing interval. These results may suggest that lacosamide 200 mg twice/day is a useful dosing strategy for critically ill patients who require CVVH.

摘要

拉考沙胺是一种新型抗癫痫药物(AED),通过肝和肾两种机制消除。连续肾脏替代疗法(CRRT)对拉考沙胺的消除作用尚未被研究过。本病例报告的目的是描述 CRRT 环境下拉考沙胺的药代动力学。我们描述了一名因癫痫持续状态和多器官衰竭而入住研究中心的患者。该患者需要同时进行连续静脉-静脉血液滤过(CVVH)和几种 AED 治疗。在取样前,他处于稳态,每天接受两次静脉注射拉考沙胺 200mg。使用经过验证的高效液相色谱法测定血浆拉考沙胺浓度。使用 Phoenix WinNonlin 7.1 软件计算参数。稳态时的峰浓度为 7.7mg/L,谷浓度为 5.9mg/L(目标浓度为 5-12mg/L)。分布容积为 0.7L/kg,消除半衰期为 21 小时,筛系数为 0.8(±0.06)。CVVH 可清除拉考沙胺,这可通过筛系数证明,但在整个给药间隔内,血浆浓度仍保持在目标范围内。这些结果可能表明,对于需要 CVVH 的危重患者,每天两次 200mg 的拉考沙胺剂量是一种有效的治疗策略。

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