a Department of Pediatrics , University of L'Aquila , L'Aquila , Italy.
b Child Neurology and Psychiatry Unit , Children's Hospital G. Salesi , Ancona , Italy.
Expert Opin Drug Metab Toxicol. 2019 Mar;15(3):199-211. doi: 10.1080/17425255.2019.1575361. Epub 2019 Feb 7.
Epilepsy is a chronic and debilitating neurological disease, with a peak of incidence in the first years of life. Today, the vast armamentarium of antiepileptic drugs (AEDs) available make even more challenging to select the most appropriate AED and establish the most effective dosing regimen. In fact, AEDs pharmacokinetics is under the influence of important age-related factors which cannot be ignored. Areas covered: Physiological changes occurring during development age (different body composition, immature metabolic patterns, reduced renal activity) can significantly modify the pharmacokinetic profile of AEDs (adsorption, volume of distribution, half-life, clearance), leading to an altered treatment response. We reviewed the main pharmacokinetic characteristics of AEDs used in children, focusing on age-related factors which are of relevance when treating this patient population. Expert opinion: To deal with this pharmacokinetic variability, physicians have at their disposal two tools: 1) therapeutic drug concentration monitoring, which may help to set the optimal therapeutic regimen for each patient and to monitor eventual fluctuation, and 2) the use of extended-release drug formulations, when available. In the next future, the development of 'ad-hoc' electronic dashboard systems will represent relevant decision-support tools making the AED therapy even more individualized and precise, especially in children.
癫痫是一种慢性、使人虚弱的神经系统疾病,发病高峰期在生命的头几年。如今,大量的抗癫痫药物(AEDs)可供选择,这使得选择最合适的 AED 并制定最有效的剂量方案变得更加具有挑战性。事实上,AEDs 的药代动力学受到许多不可忽视的重要年龄相关因素的影响。
在发育年龄期间发生的生理变化(不同的身体成分、不成熟的代谢模式、肾脏活动减少)可显著改变 AEDs 的药代动力学特征(吸收、分布容积、半衰期、清除率),导致治疗反应改变。我们回顾了用于儿童的 AED 的主要药代动力学特征,重点关注与治疗该患者群体相关的年龄相关因素。
为了应对这种药代动力学的可变性,医生有两种工具可供使用:1)治疗药物浓度监测,这有助于为每个患者设定最佳治疗方案,并监测可能的波动;2)在有条件的情况下使用延长释放药物制剂。在未来,“定制”电子仪表板系统的开发将成为重要的决策支持工具,使 AED 治疗更加个体化和精确,尤其是在儿童中。