Swami Rajan, Shahiwala Aliasgar
, House no. 1089, Sector 20 B, Chandigarh, 160020, India,
Eur J Drug Metab Pharmacokinet. 2013 Dec;38(4):231-9. doi: 10.1007/s13318-013-0126-0. Epub 2013 Apr 14.
Physicochemical properties, such as molecular weight, size, partition coefficient, acid dissociation constant and solubility have a great impact on pharmacokinetics of traditional small molecule drugs and substantially used in development of small drugs. However, predicting pharmacokinetic fate (absorption, distribution, metabolism and elimination) of protein therapeutics from their physicochemical parameters is extremely difficult due to the macromolecular nature of therapeutic proteins and peptides. Their structural complexity and immunogenicity are other contributing factors that determine their biological fate. Therefore, to develop generalized strategies concerning development of therapeutic proteins and peptides are highly challenging. However, reviewing the literature, authors found that physiochemical properties, such as molecular weight, charge and structural modification are having great impact on pharmacokinetics of protein therapeutics and an attempt is made to provide the major findings in this manuscript. This manuscript will serve to provide some bases for developing protein therapeutics with desired pharmacokinetic profile.
物理化学性质，如分子量、大小、分配系数、酸解离常数和溶解度，对传统小分子药物的药代动力学有很大影响，并在小分子药物的研发中大量应用。然而，由于治疗性蛋白质和肽的大分子性质，从其物理化学参数预测蛋白质治疗药物的药代动力学命运（吸收、分布、代谢和消除）极其困难。它们的结构复杂性和免疫原性是决定其生物学命运的其他因素。因此，制定关于治疗性蛋白质和肽开发的通用策略极具挑战性。然而，通过查阅文献，作者发现分子量、电荷和结构修饰等物理化学性质对蛋白质治疗药物的药代动力学有很大影响，并试图在本手稿中提供主要研究结果。本手稿将为开发具有理想药代动力学特征的蛋白质治疗药物提供一些依据。
