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

不稳定的 AED 水平对老年疗养院癫痫患者的临床影响

• 批准号: 7917240
• 负责人: ANGELA K BIRNBAUM
• 金额: $ 41.85万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7917240
• 关键词: Accident and Emergency department; Activities of Daily Living; Adverse effects; Adverse event; Antidepressive Agents; Antiepileptic Agents; Ataxia; Beds; Blood; Calcium Channel Blockers; Censuses; Clinical; Clinical Management; Cognition; Concentration measurement; Cytochrome P450; Data; Direct Costs; Dose; Drug Costs; Drug Formulations; Drug Kinetics; Drug usage; Elderly; Enrollment; Enzymes; Epilepsy; Exhibits; Foundations; Fracture; Frequencies; Gene Mutation; Geriatric Assessment; Geriatric Nursing; Goals; Half-Life; Hospitalization; Individual; Kidney; Kinetics; Lead; Levetiracetam; Long-Term Care; Measures; Metabolic; Metabolism; Monitor; New York; Nurses; Nursing Homes; Outcome; Outcome Measure; Pathologic Nystagmus; Patients; Persons; Pharmaceutical Preparations; Pharmacotherapy; Phenytoin; Population; Quality of life; Recruitment Activity; Reporting; Research Personnel; Seizures; Serum; Site; Techniques; Testing; Therapeutic; Time; Toxic effect; United States; Variant; Visit; Water; adverse outcome; alertness; cost; cost effectiveness; cost utility analysis; evidence based guidelines; experience; falls; health related quality of life; innovation; instrument; lamotrigine; national surveillance; novel; pharmacokinetic characteristic; programs; prospective; response; surveillance study; young adult

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.

描述（由申请人提供）：尽管苯妥英（PHT）被认为会导致老年人跌倒，并且由于其复杂的药代动力学而难以服用，但它仍然是疗养院中最常开出的抗癫痫药物（AED），有 6%大约有 150 万美国居民接收该病毒。 PHT 是一种很难剂量获得最佳治疗效果的 AED，因为它的消除动力学是非线性的，它在患者体内的浓度可能变化很大（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。拉莫三嗪 (LTG) 和左乙拉西坦 (LEV) 等新型 AED 似乎具有更理想的药代动力学特征，并且使用它们可能会比使用 PHT 产生更好的结果。然而，没有关于疗养院使用 AED 的结果、指导管理的 AED 浓度的正确使用，以及使用较旧的 AED 与较新的更昂贵的 AED 的成本效益的信息。我们的小组发现，即使剂量和联合用药没有变化，许多疗养院患者的 PHT 浓度也会出现明显波动。这些患者中 64.3% 的波动大于 5 ug/ml，据报道这一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收集接受 PHT、LTG 和 LEV 治疗的老年疗养院居民抽血时的前瞻性结果信息（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，并确定总成本（药物、疗养院环境中 AED 治疗的住院次数、护理时间等）。我们在两个地理区域（明尼阿波利斯和纽约）招募了四个主要疗养院地点，对 7,000 多名居民进行了床位普查。我们将招募 200 名疗养院居民接受 AED 治疗，以获得由 175 名受试者组成的研究组（50 LEV、50 LTG、75 PHT）。将在大约 9 个月的时间内对它们进行五次研究。该项目的长期目标是为创建第一个关于疗养院居民使用 AED 的循证建议奠定基础。