Russo Emilio, Citraro Rita, Mula Marco
a Science of Health Department, School of Medicine and Surgery , University of Catanzaro , Catanzaro , Italy.
b Atkinson Morley Regional Neuroscience Centre , St George's University Hospitals NHS Foundation Trust , London , UK.
Expert Opin Drug Discov. 2017 Nov;12(11):1169-1178. doi: 10.1080/17460441.2017.1366985. Epub 2017 Aug 23.
Brivaracetam (BRV) is a new AED currently licensed for the adjunctive treatment of adult patients with focal epilepsies. It is a ligand of the ubiquitous synaptic vesicle glycoprotein 2A (SV2A). Areas covered: This paper covers the preclinical and subsequent clinical development of BRV focusing on the discovery of the SV2A protein as the main target for levetiracetam (LEV) and the main similarities and differences between LEV and BRV in terms of pharmacodynamic and pharmacokinetic properties. Phase II and Phase III studies are also presented and data from post-marketing phase IV studies are discussed. Expert opinion: The preclinical development of BRV is quite unique and has raised several doubts on current methodologies adopted for AED development, reinforcing the need for new approaches. The preclinical and clinical profile suggest that BRV is potentially an ideal compound in the emergency setting given the rapid onset of action associated with being water soluble and, therefore, available in intravenous formulation. In addition, data from Phase III studies have already suggested that BRV may be effective not only in focal epilepsies but also in generalised syndromes. Further data from special populations such as children and women of child bearing age are urgently needed.
布立伏胺（BRV）是一种新型抗癫痫药物（AED），目前已获许可用于成人局灶性癫痫的辅助治疗。它是普遍存在的突触囊泡糖蛋白2A（SV2A）的配体。涵盖领域：本文涵盖了布立伏胺的临床前及后续临床开发，重点关注作为左乙拉西坦（LEV）主要靶点的SV2A蛋白的发现，以及左乙拉西坦和布立伏胺在药效学和药代动力学特性方面的主要异同。还介绍了II期和III期研究，并讨论了上市后IV期研究的数据。专家观点：布立伏胺的临床前开发相当独特，引发了对当前抗癫痫药物开发所采用方法的诸多质疑，凸显了采用新方法的必要性。临床前和临床资料表明，鉴于布立伏胺起效迅速且具有水溶性，因此有静脉制剂，它在紧急情况下可能是一种理想的化合物。此外，III期研究的数据已表明，布立伏胺不仅可能对局灶性癫痫有效，对全身性癫痫综合征也可能有效。迫切需要来自儿童和育龄妇女等特殊人群的更多数据。
