Birnbaum Angela K
Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Int Rev Neurobiol. 2007;81:211-20. doi: 10.1016/S0074-7742(06)81013-5.
With approximately 10% of elderly nursing home residents taking antiepileptic drugs (AEDs), it is critical to understand the pharmacokinetics, dosing, and possible adverse reactions of these AEDs. In this chapter, five AEDs commonly prescribed to nursing home residents will be discussed. Phenytoin (PHT), the most commonly used AED in this population, is extensively metabolized by the cytochrome P450 enzyme system, is highly protein bound, and interacts with many concomitant medications. Up to 45% of nursing home residents who receive PHT have concentrations below the range (subtherapeutic) used in adults (<65 years), while approximately 10% of residents have concentrations that are potentially toxic (>20 microg/ml). In addition, serum PHT concentrations can vary greatly within an individual resident and may be subtherapeutic one day and potentially toxic the next. Valproic acid is taken by approximately 9-17% of nursing home residents who are administered AEDs, with over half using it for nonseizure indications. Doses are approximately 16 mg/kg/day in elderly nursing home residents, but doses and serum concentrations are lower in the oldest age group (> or =85 years). A majority of residents are maintained at serum concentrations considered subtherapeutic for epilepsy, whereas relatively few (approximately 3%) are maintained at toxic levels. The average (+/-SD) carbamazepine (CBZ) dose is 8.8 +/- 4.7 mg/kg/day, yielding a mean serum concentration of 6.3 +/- 2.2 mg/liter. Subtherapeutic concentrations are found in up to 20% of serum measurements, while 2.5% of serum measurements are in the toxic range. CBZ is highly bound to serum albumin and alpha1-acid glycoprotein and is metabolized to carbamazepine-10,11-epoxide, an active metabolite thought to be responsible for some side effects. Phenobarbital (PB) is frequently combined with PHT. This combination can cause devastating side effects because both PB and PHT can produce cognitive side effects. Gabapentin is one of the newer AEDs frequently administered to nursing home residents. Its lack of both hepatic metabolism and protein binding potentially makes it a safer drug in this population.
约10%的老年疗养院居民服用抗癫痫药物（AEDs），因此了解这些AEDs的药代动力学、剂量及可能的不良反应至关重要。在本章中，将讨论通常开给疗养院居民的五种AEDs。苯妥英（PHT）是该人群中最常用的AED，通过细胞色素P450酶系统广泛代谢，高度与蛋白结合，并与许多同时服用的药物相互作用。接受PHT治疗的疗养院居民中，高达45%的人血药浓度低于成人（<65岁）使用的范围（治疗不足），而约10%的居民血药浓度具有潜在毒性（>20μg/ml）。此外，个体居民的血清PHT浓度可能差异很大，可能一天治疗不足，第二天就有潜在毒性。约9 - 17%接受AEDs治疗的疗养院居民服用丙戊酸，其中超过一半用于非癫痫适应症。老年疗养院居民的剂量约为16mg/kg/天，但年龄最大组（≥85岁）的剂量和血药浓度较低。大多数居民的血药浓度维持在被认为对癫痫治疗不足的水平，而相对较少（约3%）维持在中毒水平。卡马西平（CBZ）的平均（±标准差）剂量为8.8±4.7mg/kg/天，平均血清浓度为6.3±2.2mg/升。高达20%的血清检测结果显示治疗不足，而2.5%的血清检测结果处于中毒范围。CBZ高度与血清白蛋白和α1 - 酸性糖蛋白结合，并代谢为卡马西平 - 10,11 - 环氧化物，一种被认为是某些副作用原因的活性代谢物。苯巴比妥（PB）常与PHT联合使用。这种联合可能导致严重的副作用，因为PB和PHT都可产生认知副作用。加巴喷丁是经常用于疗养院居民的较新的AEDs之一。它既无肝代谢又无蛋白结合，这可能使其在该人群中成为更安全的药物。
