Clinical Impact of Unstable AED Levels in Elderly Nursing Home Epilepsy Patients

描述（由申请人提供）：尽管苯妥英（PHT）被认为是老年人跌倒的原因，而且由于复杂的药代动力学，它很难给药，但它仍然是养老院最常用的抗癫痫药物（AED），在美国大约150万居民中，有6%的人服用它。PHT是一种难以确定剂量以获得最佳治疗效果的AED，因为它的消除动力学是非线性的，其在患者体内的浓度可能非常可变（不稳定），并且它会改变该人群中使用的许多其他药物的代谢。较新的抗癫痫药，如拉莫三嗪（LTG）和左乙拉西坦（LEV）似乎具有更理想的药代动力学特征，使用它们可能比使用PHT产生更好的结果。然而，没有关于在养老院使用AED的结果的信息，正确使用AED浓度来指导管理，以及使用较旧的AED与较新的更昂贵的AED的成本效益。我们的研究小组发现，即使在剂量和联合用药没有变化的情况下，许多养老院患者体内的PHT浓度也会出现显著波动。这些患者中64.3%的波动大于5 ug/ml，据报道，这种变化会增加其他人群的癫痫发作活动。此外，许多患者的PHT浓度高于与不良事件相关的浓度。这项研究将是第一个在接受PHT、LTG和LEV治疗的养老院老人抽血时收集前瞻性结果信息（癫痫发作和不良事件）的研究。结果将有助于确定这些AED的适当水平以获得最佳结果，确定与PHT水平不稳定相关的因素，确定较新的AED是否与较少的不良事件相关，评估测量AED的有用性，并确定疗养院环境中AED治疗的总成本（药物，住院，护理时间等）。我们在两个地理区域（明尼阿波利斯和纽约）招募了四个主要的养老院，总共有7000多名居民。我们将招募200名接受AED治疗的养老院居民，形成175名受试者的研究小组（50名LEV， 50名LTG， 75名PHT）。他们将在大约9个月的时间内进行五次研究。该项目的长期目标是为养老院居民创建第一个基于证据的aed使用建议提供基础。

DESCRIPTION (provided by applicant): Although phenytoin (PHT) has been attributed to falls in the elderly and is very difficult to dose due to complicated pharmacokinetics, it continues to be the most frequently prescribed antiepileptic drug (AED) in nursing homes with 6% of the approximately 1.5 million residents in the United States receiving it. PHT is a difficult AED to dose for optimal therapeutic outcome because its elimination kinetics are nonlinear, its concentrations within a patient can be extremely variable (unstable), and it alters the metabolism of many other medications used in this population. Newer AEDs such as lamotrigine (LTG) and levetiracetam (LEV) appear to have more desirable pharmacokinetic characteristics and their use may lead to better outcomes than use of PHT. However, there is no information regarding the outcomes of AED use in nursing homes, the proper use of AED concentrations to guide management, and the cost-effectiveness of using older AEDs versus newer more expensive ones. Our group discovered that PHT concentrations fluctuate markedly within many nursing home patients even when there is no change in dose and no change in co-medications. The fluctuations in 64.3% of these patients were greater than 5 ug/ml, a change that has been reported to increase seizure activity in other populations. In addition, many patients had PHT concentrations above those that have been associated with adverse events. This study will be the first to collect prospective outcome information (seizures and adverse events) at the time of a blood draw in elderly nursing home residents treated with PHT, LTG, and LEV. Results will help define the appropriate levels of these AEDs for optimal outcomes, identify factors associated with instability of PHT levels, determine if the newer AEDs are associated with fewer adverse events, evaluate the usefulness of measuring AEDs, and determine the total costs (drug, hospitalizations, nursing time, etc.) of AED therapy in the nursing home setting. We have recruited four major nursing home sites in two geographical regions (Minneapolis and New York) with a combined bed census of over 7,000 residents. We will enroll 200 nursing home residents on AED therapy to attain a study group of 175 subjects (50 LEV, 50 LTG, 75 PHT). They will be studied five times over approximately a 9-month period. The long-term goal of this project is to provide the foundation for creating the first evidence-based recommendations for the use of AEDs for nursing home residents.