Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
Development Biologicals, Drug Metabolism And Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, US.
MAbs. 2021 Jan-Dec;13(1):1964935. doi: 10.1080/19420862.2021.1964935.
Constant technological advancement enabled the production of therapeutic monoclonal antibodies (mAbs) and will continue to contribute to their rapid expansion. Compared to small-molecule drugs, mAbs have favorable characteristics, but also more complex pharmacokinetics (PK), e.g., target-mediated nonlinear elimination and recycling by neonatal Fc-receptor. This review briefly discusses mAb biology, similarities and differences in PK processes across species and within human, and provides a detailed overview of allometric scaling approaches for translating mAb PK from preclinical species to human and extrapolating from adults to children. The approaches described here will remain vital in mAb drug development, although more data are needed, for example, from very young patients and mAbs with nonlinear PK, to allow for more confident conclusions and contribute to further growth of this field. Improving mAb PK predictions will facilitate better planning of (pediatric) clinical studies and enable progression toward the ultimate goal of expediting drug development.
不断的技术进步使治疗性单克隆抗体（mAbs）得以生产，并将继续促进其快速发展。与小分子药物相比，mAbs 具有有利的特性，但也具有更复杂的药代动力学（PK），例如，通过新生儿 Fc 受体介导的靶向非线性消除和再循环。本文简要讨论了 mAb 生物学、不同物种和人体内 PK 过程的相似性和差异，并详细概述了从临床前物种向人体转化以及从成人向儿童外推 mAb PK 的同种异体比例缩放方法。这些方法在 mAb 药物开发中仍然至关重要，尽管需要更多的数据，例如来自非常年幼的患者和具有非线性 PK 的 mAbs 的数据，以得出更有信心的结论，并为该领域的进一步发展做出贡献。改善 mAb PK 预测将有助于更好地规划（儿科）临床试验，并为实现加速药物开发的最终目标铺平道路。
