Vugmeyster Yulia, Xu Xin, Theil Frank-Peter, Khawli Leslie A, Leach Michael W
Yulia Vugmeyster, Department of Pharmacokinetics, Dynamics, and Metabolism, Pfizer Inc., Andover, MA 01810, United States.
World J Biol Chem. 2012 Apr 26;3(4):73-92. doi: 10.4331/wjbc.v3.i4.73.
Significant progress has been made in understanding pharmacokinetics (PK), pharmacodynamics (PD), as well as toxicity profiles of therapeutic proteins in animals and humans, which have been in commercial development for more than three decades. However, in the PK arena, many fundamental questions remain to be resolved. Investigative and bioanalytical tools need to be established to improve the translation of PK data from animals to humans, and from in vitro assays to in vivo readouts, which would ultimately lead to a higher success rate in drug development. In toxicology, it is known, in general, what studies are needed to safely develop therapeutic proteins, and what studies do not provide relevant information. One of the major complicating factors in nonclinical and clinical programs for therapeutic proteins is the impact of immunogenicity. In this review, we will highlight the emerging science and technology, as well as the challenges around the pharmacokinetic- and safety-related issues in drug development of mAbs and other therapeutic proteins.
在理解治疗性蛋白质在动物和人类体内的药代动力学（PK）、药效学（PD）以及毒性方面已经取得了重大进展，这些蛋白质已经进行了三十多年的商业开发。然而，在药代动力学领域，许多基本问题仍有待解决。需要建立研究和生物分析工具，以改善从动物到人类的药代动力学数据转换，以及从体外试验到体内读数的转换，这最终将提高药物开发的成功率。在毒理学方面，一般来说，已知安全开发治疗性蛋白质需要哪些研究，以及哪些研究不能提供相关信息。治疗性蛋白质的非临床和临床项目中的一个主要复杂因素是免疫原性的影响。在本综述中，我们将重点介绍新兴的科学技术，以及单克隆抗体和其他治疗性蛋白质药物开发中与药代动力学和安全性相关问题的挑战。
