Therapeutic Drug Monitoring of Lacosamide: Is 10 to 20 mg/L a Suitable Reference Range for Patients With Epilepsy?

IF 0.8 4区医学 Q4 CLINICAL NEUROLOGY

Clinical Neuropharmacology Pub Date : 2023-03-01 DOI:10.1097/WNF.0000000000000537

Sara Otero Torres, Roser Juvany Roig, Mercè Falip Centellas, Miriam Casellas Gibert, Mónica Estopiñá Antolí, Raül Rigo Bonnin, Jacint Xavier Sala-Padro, Ramón Jódar Massanés

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引用次数: 1

Abstract

Objectives: The reference range for lacosamide (LCM) has been updated from 1 to 10 mg/L to 10 to 20 mg/L. Historically, LCM range was defined from trough-level measurements, but the newer ranges were obtained from peak-level measurements. The purpose of the study was to evaluate the relationship between LCM plasma levels higher than 10 mg/L and the incidence of adverse effects.

Methods: This was a single-center, retrospective, observational study of adult outpatients with epilepsy who were prescribed LCM and had LCM serum concentrations (LCM-SCs) >10 mg/L on drug-fasting samples, measured from June 2017 to December 2020.

Results: A total of 55 LCM-SC samples corresponding to 44 patients (25 women [57%]) were analyzed. The median age was 47 (39-61) years. The median LCM-SC was 13.4 (11.2-17.8) mg/L. Adverse effects were reported in 18 patients (41%). Forty-eight percent (21 of 44) of patients required an LCM dose reduction, with a mean LCM-SC of 16.0 (13.2-18.1) mg/L, whereas, in the remaining patients (23 of 44), LCM dose was not modified, with a mean LCM-SC of 12.2 (10.7-14.2) mg/L ( P = 0.0244). Forty-one percent (18 of 44) of patients reported adverse effects related to LCM, with a mean LCM-SC of 15.6 (12.7-18.4) mg/L, whereas, in the remaining patients (26 of 44), adverse effects did not occur, with a mean LCM-SC of 12.6 (10.7-16.5) mg/L ( P = 0.0495).

Conclusions: The 10 to 20 mg/L reference range clearly increases toxicity in patients treated with LCM. Adjusting the reference range upper limit to 12 mg/L with a routine therapeutic drug monitoring program is suggested, to achieve a reasonable probability of efficacy and decrease toxicity.

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拉科沙胺治疗药物监测:10 ~ 20mg /L是癫痫患者合适的参考范围吗?

目的:拉科沙胺(LCM)的参考范围从1 ~ 10mg /L更新为10 ~ 20mg /L。从历史上看，LCM范围是从低谷电平测量中定义的，但较新的范围是从峰值电平测量中获得的。本研究的目的是评估LCM血浆浓度高于10 mg/L与不良反应发生率之间的关系。方法:这是一项单中心、回顾性、观察性研究，研究对象是2017年6月至2020年12月期间服用LCM且LCM血清浓度(LCM- scs) >10 mg/L的空腹药物样本的成年门诊癫痫患者。结果:共分析了44例患者(25例女性，57%)的55份LCM-SC样本。中位年龄为47岁(39-61岁)。中位LCM-SC为13.4 (11.2-17.8)mg/L。18例(41%)患者报告了不良反应。48%的患者(44名中的21名)需要减少LCM剂量，平均LCM- sc为16.0 (13.2-18.1)mg/L，而其余患者(44名中的23名)LCM剂量没有改变，平均LCM- sc为12.2 (10.7-14.2)mg/L (P = 0.0244)。41%(44名患者中的18名)报告了与LCM相关的不良反应，平均LCM- sc为15.6 (12.7-18.4)mg/L，而其余患者(44名患者中的26名)未发生不良反应，平均LCM- sc为12.6 (10.7-16.5)mg/L (P = 0.0495)。结论:10 ~ 20mg /L的参考范围明显增加LCM患者的毒性。建议将参考范围上限调整为12mg /L，并采用常规治疗药物监测方案，以达到合理的疗效概率和降低毒性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Neuropharmacology 医学-临床神经学

CiteScore

1.20

自引率

10.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Clinical Neuropharmacology is a peer-reviewed journal devoted to the pharmacology of the nervous system in its broadest sense. Coverage ranges from such basic aspects as mechanisms of action, structure-activity relationships, and drug metabolism and pharmacokinetics, to practical clinical problems such as drug interactions, drug toxicity, and therapy for specific syndromes and symptoms. The journal publishes original articles and brief reports, invited and submitted reviews, and letters to the editor. A regular feature is the Patient Management Series: in-depth case presentations with clinical questions and answers.