Ezan Eric, Becher François, Fenaille François
CEA, iBEB (Institut de Biologie Environnementale et Biotechnologie) , Bagnols-sur-Cèze , France +33 04 66 79 19 04 ; +33 04 66 79 19 08 ;
Expert Opin Drug Metab Toxicol. 2014 Aug;10(8):1079-91. doi: 10.1517/17425255.2014.925878. Epub 2014 Jun 4.
In the last decade, our increased knowledge of factors governing the pharmacokinetics and metabolism of biologics (recombinant therapeutic proteins) has driven, and will continue to support, biological engineering and the design of delivery systems for more efficient biologics. Further research in analytical methods for assessing their in vitro and/or in vivo metabolism will also support these developments.
In this review we will discuss the main components affecting the metabolism of biologics, and try to demonstrate how novel analytical evaluations will facilitate their future development. We will focus on the use of radiolabeled drugs, ligand-binding assays and mass spectrometry.
Future marketed biologics will be complex structures, such as glycoengineered, fused, or chemically modified proteins. Their in vivo efficiencies will be strongly dependent on their metabolic stabilities. Similarly to small molecular drugs, for which in vitro and in vivo biochemical platforms and analytical techniques have helped to rationalize preclinical and clinical developments, we would expect this also to translate to effective approaches to study the metabolism of biologics in the near future. Mass spectrometry should emerge as a standard technique for in vivo characterization of the biotransformation products of biologics.
在过去十年中，我们对影响生物制品（重组治疗性蛋白质）药代动力学和代谢的因素的认识不断增加，这推动了生物工程以及更高效生物制品递送系统的设计，并且将继续提供支持。对评估其体外和/或体内代谢的分析方法的进一步研究也将支持这些发展。
在本综述中，我们将讨论影响生物制品代谢的主要因素，并试图展示新颖的分析评估将如何促进其未来发展。我们将重点关注放射性标记药物、配体结合分析和质谱的应用。
未来上市的生物制品将是复杂的结构，例如糖基工程化、融合或化学修饰的蛋白质。它们在体内的效率将强烈依赖于其代谢稳定性。与小分子药物类似，体外和体内生化平台以及分析技术有助于使小分子药物的临床前和临床开发合理化，我们预计在不久的将来这也将转化为研究生物制品代谢的有效方法。质谱应该会成为体内表征生物制品生物转化产物的标准技术。
