EFFICACY & METABOLISM OF ANTICONVULSANTS IN NEONATES

功效

• 批准号: 3413098
• 负责人: MICHAEL James PAINTER
• 金额: $ 13.43万
• 依托单位: MAGEE-WOMEN'S HOSPITAL OF UPMC
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-04-01 至 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3413098
• 关键词: anticonvulsants; cardiovascular function; dosage; drug adverse effect; drug metabolism; electroencephalography; generalized seizures; high performance liquid chromatography; human subject; human therapy evaluation; newborn human (0-6 weeks); patient monitoring device; phenobarbital; phenytoin; radioassay; respiratory function

Neonatal seizures are a frequent problem encountered in neonatal nurseries, but their significance is controversial. Some investigators regard newborn seizures as simply epiphenomena and reflective of brain injury while others note associated metabolic and physiologic aberrations implying that seizures per se are injurious to the central nervous system. Despite the controversy, current standards are such that seizures are treated, but the choice of anticonvulsants has not been on the documented superiority of one agent over another. Small numbers of patients treated without EEG confirmation or careful attention to toxicity have formed the rationale for treating neonatal seizures. Several treatment regimens have been advanced but the two drugs most commonly chosen are phenobarbital and phenytoin. We propose to evaluate the relative efficacies of phenobarbital and phenytoin in the treatment of neonatal seizures utilizing EEG criteria for the diagnosis and response to therapy, but also recording and charting the course of clinically noted abnormal movements. This study will achieve free levels of 25 mg/L for phenobarbital and 3mg/L for phenytoin. The study will be performed over five years in a single institution enrolling twenty infants yearly. Fifty infants in each group will be randomized to phenobarbital or phenytoin therapy. Because of marked variations in the binding of phenobarbital and phenytoin discovered in preliminary studies, in vitro binding analysis performed prior determination of plasma free and bound levels will allow a judgement of whether desired therapy will be judged at 60 minutes. If no adjustment is necessary, response to therapy will be judged at 60 minutes, and at 120 minutes if a dose adjustment is required. Continuous EEG monitoring will be performed for the first 24 hours of the study. The aim of therapy will be complete cessation of seizures, but following optimum use of these anticonvulsants a scale will be used to assess graded differences in therapeutic response to the drugs. Respiratory and cardiovascular parameters of toxicity will be studied. Alterations of plasma concentrations of factors known to affect binding will be studied. This study will be the first to assess the efficacy of the two most common drugs used in the treatment of neonatal seizures. The data obtained will have important implications for treatment regimens and form a basis for the subsequent evaluations of agents used in treating neonatal seizures.

新生儿癫痫发作是在新生儿托儿所遇到的常见问题， 但是它们的意义是有争议的。 一些调查人员认为新生儿 癫痫发作仅仅是epiphenomena，反映了脑损伤，而其他人则反映 注意相关的代谢和生理畸变，暗示着 癫痫发作本身对中枢神经系统有害。 尽管有 争议，目前的标准是癫痫发作的，但是 抗惊厥药的选择尚未在一个被证明的优势 代理另一个。 未经脑电图治疗的少数患者 确认或仔细注意毒性已经形成了 治疗新生儿癫痫发作。 已经采取了几种治疗方案 但是最常见的两种药物是苯巴比妥和苯妥英。 我们建议评估苯巴比妥和 利用脑电图标准的新生儿癫痫发作的苯妥英 对治疗的诊断和反应，但还记录和绘制了 临床上注意到的异常运动过程。 这项研究将实现 苯巴比妥的25 mg/L的自由水平，苯妥英和3mg/L的自由水平。 这 研究将在单个机构注册的五年内进行 每年二十个婴儿。 每组中的五十名婴儿将被随机分为 苯巴比妥或苯妥英疗法。 由于明显的变化 在初步研究中发现的苯巴比妥和苯妥英的结合， 体外结合分析事先确定了缺乏血浆和 约束水平将允许判断是否需要进行所需的治疗 在60分钟内进行评判。 如果不需要调整，请反应治疗 将在60分钟内进行评判，如果调整剂量 必需的。 将对前24个进行连续的脑电图监测 研究小时。 治疗的目的是完全停止 癫痫发作，但在最佳使用这些抗惊厥药后，量表将 用于评估对药物治疗反应的分级差异。 将研究毒性的呼吸和心血管参数。 已知影响结合的因素的血浆浓度的改变 将被研究。 这项研究将是第一个评估的功效 用于治疗新生儿癫痫发作的两种最常见的药物。 这 获得的数据将对治疗方案和 构成对治疗代理的随后评估的基础 新生儿癫痫发作。