Landmark Cecilie Johannessen, Johannessen Svein I, Tomson Torbjörn
Programme for Pharmacy, Dept. of Life Sciences and Health, Oslo and Akershus University College of Applied Sciences, Oslo, Norway, The National Center for Epilepsy, Sandvika, Oslo University Hospital, Norway, Dept. of Pharmacology, Oslo University Hospital, Norway.
The National Center for Epilepsy, Sandvika, Oslo University Hospital, Norway, Dept. of Pharmacology, Oslo University Hospital, Norway.
Epileptic Disord. 2016 Dec 1;18(4):367-383. doi: 10.1684/epd.2016.0880.
This review focuses on the evolution of approaches to dosing of antiepileptic drugs (AEDs) in clinical practice through history. There has been a shift in the view of treatment of epilepsy, from "one dose fits all patients" in the early days to individualisation of treatment. Over the past 50 years, our knowledge of pharmacological variability of AEDs has markedly increased through implementation of therapeutic drug monitoring (TDM). The use of TDM has demonstrated extensive pharmacokinetic variability for AEDs and a need to individualise the treatment for an optimal outcome. Factors that contribute to pharmacokinetic variability include external factors (including food and comedication), physiological factors (gender, age, and pregnancy), pathological conditions (organ dysfunction), and genetic factors (polymorphisms in metabolising enzymes). Patient groups of children, pregnant women, and the elderly, in whom the most extensive pharmacokinetic changes occur, need special attention and close follow-up of treatment. Patients with complicated and changing combination treatments are also vulnerable. Therapeutic drug monitoring may be particularly helpful in such situations. There are also challenges regarding the use and misuse of therapeutic drug monitoring, such as the use of drug monitoring without a clear indication, misinterpretation of the reference range, and erroneous sampling times.
本综述着重介绍了抗癫痫药物（AEDs）临床用药方法随历史发展的演变。癫痫治疗观念已发生转变，从早期的“一种剂量适用于所有患者”转变为个体化治疗。在过去50年里，通过实施治疗药物监测（TDM），我们对AEDs药物代谢差异的了解显著增加。TDM的应用已证明AEDs存在广泛的药代动力学差异，且需要个体化治疗以获得最佳疗效。导致药代动力学差异的因素包括外部因素（包括食物和合并用药）、生理因素（性别、年龄和妊娠）、病理状况（器官功能障碍）以及遗传因素（代谢酶的多态性）。儿童、孕妇和老年人等患者群体，其药代动力学变化最为广泛，需要特别关注并密切随访治疗情况。接受复杂且不断变化的联合治疗的患者也较为脆弱。治疗药物监测在这种情况下可能特别有用。在治疗药物监测的使用和滥用方面也存在挑战，例如在没有明确指征的情况下使用药物监测、对参考范围的错误解读以及错误的采样时间。
