癫痫中抗癫痫药物的治疗药物监测：2018年更新

Therapeutic Drug Monitoring of Antiepileptic Drugs in Epilepsy: A 2018 Update.

作者信息

Patsalos Philip N, Spencer Edgar P, Berry Dave J

机构信息

Epilepsy Society, Therapeutic Drug Monitoring Unit, Chalfont Centre for Epilepsy, Chalfont St Peter, Buckinghamshire.

Department of Clinical and Experimental Epilepsy, UCL-Institute of Neurology, Queen Square, London, United Kingdom.

出版信息

Ther Drug Monit. 2018 Oct;40(5):526-548. doi: 10.1097/FTD.0000000000000546.

DOI:10.1097/FTD.0000000000000546

PMID:29957667

Abstract

BACKGROUND

Antiepileptic drugs (AEDs) are the mainstay of epilepsy treatment. Since 1989, 18 new AEDs have been licensed for clinical use and there are now 27 licensed AEDs in total for the treatment of patients with epilepsy. Furthermore, several AEDs are also used for the management of other medical conditions, for example, pain and bipolar disorder. This has led to an increasingly widespread application of therapeutic drug monitoring (TDM) of AEDs, making AEDs among the most common medications for which TDM is performed. The aim of this review is to provide an overview of the indications for AED TDM, to provide key information for each individual AED in terms of the drug's prescribing indications, key pharmacokinetic characteristics, associated drug-drug pharmacokinetic interactions, and the value and the intricacies of TDM for each AED. The concept of the reference range is discussed as well as practical issues such as choice of sample types (total versus free concentrations in blood versus saliva) and sample collection and processing.

METHODS

The present review is based on published articles and searches in PubMed and Google Scholar, last searched in March 2018, in addition to references from relevant articles.

RESULTS

In total, 171 relevant references were identified and used to prepare this review.

CONCLUSIONS

TDM provides a pragmatic approach to epilepsy care, in that bespoke dose adjustments are undertaken based on drug concentrations so as to optimize clinical outcome. For the older first-generation AEDs (carbamazepine, ethosuximide, phenobarbital, phenytoin, primidone, and valproic acid), much data have accumulated in this regard. However, this is occurring increasingly for the new AEDs (brivaracetam, eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, piracetam, pregabalin, rufinamide, stiripentol, sulthiame, tiagabine, topiramate, vigabatrin, and zonisamide).

摘要

背景

抗癫痫药物（AEDs）是癫痫治疗的主要手段。自1989年以来，已有18种新型AEDs获批用于临床，目前共有27种获批的AEDs用于治疗癫痫患者。此外，几种AEDs还用于治疗其他疾病，例如疼痛和双相情感障碍。这导致AEDs的治疗药物监测（TDM）应用日益广泛，使AEDs成为进行TDM最常见的药物之一。本综述的目的是概述AED TDM的适应证，针对每种AED提供有关药物处方适应证、关键药代动力学特征、相关药物 - 药物药代动力学相互作用以及每种AED的TDM价值和复杂性的关键信息。还讨论了参考范围的概念以及诸如样本类型选择（血液与唾液中的总浓度与游离浓度）和样本采集与处理等实际问题。

方法

本综述基于已发表的文章以及在PubMed和谷歌学术上的检索结果（最后一次检索于2018年3月），此外还参考了相关文章的参考文献。

结果

总共识别出171篇相关参考文献并用于撰写本综述。

结论

TDM为癫痫治疗提供了一种实用方法，即根据药物浓度进行定制剂量调整以优化临床疗效。对于较老的第一代AEDs（卡马西平、乙琥胺、苯巴比妥、苯妥英、扑米酮和丙戊酸），在这方面已经积累了大量数据。然而，对于新型AEDs（布瓦西坦、醋酸艾司利卡西平、非氨酯、加巴喷丁、拉科酰胺、拉莫三嗪、左乙拉西坦、奥卡西平、吡仑帕奈、吡拉西坦、普瑞巴林、卢非酰胺、司替戊醇、舒噻美、替加宾、托吡酯、氨己烯酸和唑尼沙胺），这种情况也越来越普遍。