Pharmacology & Clinical Pharmacology Lab, College of Medicine, Hanyang University, Seoul 133-791, Korea.
Korean J Physiol Pharmacol. 2011 Apr;15(2):67-81. doi: 10.4196/kjpp.2011.15.2.67. Epub 2011 Apr 30.
Epilepsy is a chronic disease occurring in approximately 1.0% of the world's population. About 30% of the epileptic patients treated with availably antiepileptic drugs (AEDs) continue to have seizures and are considered therapy-resistant or refractory patients. The ultimate goal for the use of AEDs is complete cessation of seizures without side effects. Because of a narrow therapeutic index of AEDs, a complete understanding of its clinical pharmacokinetics is essential for understanding of the pharmacodynamics of these drugs. These drug concentrations in biological fluids serve as surrogate markers and can be used to guide or target drug dosing. Because early studies demonstrated clinical and/or electroencephalographic correlations with serum concentrations of several AEDs, It has been almost 50 years since clinicians started using plasma concentrations of AEDs to optimize pharmacotherapy in patients with epilepsy. Therefore, validated analytical method for concentrations of AEDs in biological fluids is a necessity in order to explore pharmacokinetics, bioequivalence and TDM in various clinical situations. There are hundreds of published articles on the analysis of specific AEDs by a wide variety of analytical methods in biological samples have appears over the past decade. This review intends to provide an updated, concise overview on the modern method development for monitoring AEDs for pharmacokinetic studies, bioequivalence and therapeutic drug monitoring.
癫痫是一种在全球约 1.0%的人群中发生的慢性疾病。大约 30%的接受现有抗癫痫药物 (AED) 治疗的癫痫患者仍有发作,被认为是治疗抵抗或难治性患者。使用 AED 的最终目标是在没有副作用的情况下完全停止发作。由于 AED 的治疗指数较窄,因此完全了解其临床药代动力学对于理解这些药物的药效动力学至关重要。这些生物体液中的药物浓度可作为替代标志物,并可用于指导或靶向药物剂量。由于早期的研究表明几种 AED 的血清浓度与临床和/或脑电图有相关性,因此近 50 年来,临床医生开始使用 AED 的血浆浓度来优化癫痫患者的药物治疗。因此,为了在各种临床情况下探索药代动力学、生物等效性和治疗药物监测,有必要建立用于生物体液中 AED 浓度的验证分析方法。在过去的十年中,已经有数百篇关于在生物样本中通过各种分析方法分析特定 AED 的文章发表。这篇综述旨在为用于药代动力学研究、生物等效性和治疗药物监测的 AED 监测的现代方法开发提供一个更新、简洁的概述。