Department of Pharmaceutics, University of Florida, Gainesville, FL, USA.
J Clin Pharmacol. 2013 Oct;53(10):1058-71. doi: 10.1002/jcph.143. Epub 2013 Aug 1.
Development of central nervous system-acting drugs would be enhanced by suitable biomarkers that reflect the targeted pathophysiologic brain state. The electroencephalogram (EEG) has several characteristics of an ideal biomarker and can be promptly adapted to pre-clinical and clinical testing. The aim of this study was to evaluate EEG as a measure of the wakefulness-promoting effect of armodafinil in sleep deprived healthy subjects. Armodafinil pharmacodynamics were simultaneously assessed by EEG- and behavioral-based measures including a well-established measure of alertness. Using two quantitative EEG-based measures-power spectral and event-related brain activity analyses-we observed that armodafinil mitigated the slowing of brain activity and the decrease of the event-related brain activity caused by sleep deprivation. Armodafinil-induced changes in EEG are in agreement and explain up to 73.1% of the armodafinil-induced changes in alertness. Our findings suggest that EEG can serve as a marker of the wakefulness-promoting drug effect.
开发作用于中枢神经系统的药物将通过合适的生物标志物得到加强,这些标志物反映了靶向的病理生理脑状态。脑电图(EEG)具有作为理想生物标志物的几个特征,并且可以迅速适应临床前和临床测试。本研究的目的是评估 EEG 作为评估在睡眠剥夺的健康受试者中促进觉醒的阿莫达非尼作用的测量方法。同时通过 EEG 和基于行为的测量方法(包括经过验证的警觉性测量方法)评估阿莫达非尼的药效动力学。使用两种基于定量 EEG 的测量方法——功率谱和事件相关脑活动分析——我们观察到,阿莫达非尼减轻了睡眠剥夺引起的脑活动减慢和事件相关脑活动的减少。脑电图诱导的变化与警觉性诱导的变化一致,解释了高达 73.1%的阿莫达非尼诱导的警觉性变化。我们的研究结果表明,脑电图可以作为促进觉醒药物作用的标志物。