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生物制药的药代动力学:它们在分子设计中的关键作用。

Pharmacokinetics of Biopharmaceuticals: Their Critical Role in Molecular Design.

作者信息

Ogihara Takuo, Mizoi Kenta, Ishii-Watabe Akiko

机构信息

Laboratory of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki 370-0033, Japan.

Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki 370-0033, Japan.

出版信息

Biomedicines. 2023 May 16;11(5):1456. doi: 10.3390/biomedicines11051456.

Abstract

Biopharmaceuticals have developed rapidly in recent years due to the remarkable progress in gene recombination and cell culture technologies. Since the basic structure of biopharmaceuticals can be designed and modified, it is possible to control the duration of action and target specific tissues and cells by kinetic modification. Amino acid sequence modifications, albumin fusion proteins, polyethylene glycol (PEG) modifications, and fatty acid modifications have been utilized to modify the duration of action control and targeting. This review first describes the position of biopharmaceuticals, and then the kinetics (absorption, distribution, metabolism, elimination, and pharmacokinetics) of classical biopharmaceuticals and methods of drug quantification. The kinetic innovations of biopharmaceuticals are outlined, including insulin analog, antibody-related drugs (monoclonal antibodies, Fab analogs, Fc analogs, Fab-PEG conjugated proteins, antibody-drug conjugates, etc.), blood coagulation factors, interferons, and other related drugs. We hope that this review will be of use to many researchers interested in pharmaceuticals derived from biological components, and that it aids in their knowledge of the latest developments in this field.

摘要

近年来,由于基因重组和细胞培养技术取得了显著进展,生物制药发展迅速。由于生物制药的基本结构可以设计和修饰,因此通过动力学修饰来控制作用持续时间并靶向特定组织和细胞成为可能。氨基酸序列修饰、白蛋白融合蛋白、聚乙二醇(PEG)修饰和脂肪酸修饰已被用于修饰作用持续时间的控制和靶向。本综述首先介绍生物制药的地位,然后阐述经典生物制药的动力学(吸收、分布、代谢、消除和药代动力学)以及药物定量方法。概述了生物制药的动力学创新,包括胰岛素类似物、抗体相关药物(单克隆抗体、Fab类似物、Fc类似物、Fab-PEG缀合蛋白、抗体-药物缀合物等)、凝血因子、干扰素及其他相关药物。我们希望这篇综述对许多对源自生物成分的药物感兴趣的研究人员有所帮助,并有助于他们了解该领域的最新进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fa2/10216213/f78b89af1283/biomedicines-11-01456-g001.jpg

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