Palliative Care Clinic, Sanatorio Médica Uruguaya, Montevideo, Uruguay.
Department of Pharmaceutical Sciences, Faculty of Chemistry, Therapeutic Drug Monitoring Service, Hospital de Clínicas, Universidad de la República, Montevideo, Uruguay.
J Palliat Med. 2021 Feb;24(2):248-251. doi: 10.1089/jpm.2019.0525. Epub 2020 Apr 8.
Seizure control is challenging in the palliative care setting. Subcutaneous (SC) levetiracetam (LEV) is currently an off-label route of administration and effectiveness, tolerability, and pharmacokinetics studies for this route are scarce. This prospective study aimed at evaluating effectiveness and tolerability of SC LEV as well as characterizing its pharmacokinetics. Patients ( = 7) who attended the palliative care clinic between September 2018 and January 2019 with diagnosis of seizures, ≥18 years, and in need of SC route of administration were included in the study. LEV plasma levels were determined using high-performance liquid chromatography and pharmacokinetic analysis were performed using Monolix 2018R2 (France). pH and osmolality of the three SC infusion solutions were also determined. Seven patients took part in the study. Seizures were controlled in six out of seven patients with doses of 1000 and 3000 mg/day. Adverse effects were mild. pH and osmolality of the SC infusion solutions were within the accepted values reported in the literature. Mean plasma LEV concentrations were 14.4 mg/L (1000 mg/day) and 27.7 mg/L (2000 mg/day). The population clearance (2.5 L/h) and the elimination half-life (10.4 hours) were successfully estimated. Based on this data, SC LEV was effective and well tolerated. Pharmacokinetic parameters for the SC route were successfully determined.
在姑息治疗环境中控制癫痫发作具有挑战性。目前，皮下（SC）左乙拉西坦（LEV）是一种超说明书的给药途径，关于该途径的有效性、耐受性和药代动力学研究很少。本前瞻性研究旨在评估 SC LEV 的有效性和耐受性，并对其药代动力学进行特征描述。2018 年 9 月至 2019 年 1 月期间，在姑息治疗诊所就诊的诊断为癫痫发作、年龄≥18 岁且需要 SC 给药途径的 7 名患者被纳入研究。使用高效液相色谱法测定 LEV 血浆水平，并使用 Monolix 2018R2（法国）进行药代动力学分析。还测定了三种 SC 输注溶液的 pH 值和渗透压。共有 7 名患者参与了这项研究。在 7 名患者中有 6 名患者的癫痫发作得到了控制，每日剂量为 1000 和 3000mg。不良反应轻微。SC 输注溶液的 pH 值和渗透压均在文献报道的可接受值范围内。平均 LEV 血浆浓度分别为 14.4mg/L（每日 1000mg）和 27.7mg/L（每日 2000mg）。成功估计了人群清除率（2.5L/h）和消除半衰期（10.4 小时）。根据这些数据，SC LEV 有效且耐受良好。成功确定了 SC 途径的药代动力学参数。
