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抗体药物偶联物研发的临床前药代动力学考量

Preclinical Pharmacokinetic Considerations for the Development of Antibody Drug Conjugates.

作者信息

Kamath Amrita V, Iyer Suhasini

机构信息

Department of Preclinical and Translational Pharmacokinetics and Pharmacodynamics, Genentech, Inc, 1 DNA Way (Mailstop 463A), South San Francisco, CA, 94080, USA.

出版信息

Pharm Res. 2015 Nov;32(11):3470-9. doi: 10.1007/s11095-014-1584-z. Epub 2014 Dec 2.

Abstract

Antibody drug conjugates (ADCs) are an emerging new class of targeted therapeutics for cancer that use antibodies to deliver cytotoxic drugs to cancer cells. There are two FDA approved ADCs on the market and over 30 ADCs in the clinical pipeline against a number of different cancer types. The structure of an ADC is very complex with multiple components and considerable efforts are ongoing to determine the attributes necessary for clinical success. Understanding the pharmacokinetics of an ADC and how it impacts efficacy and toxicity is a critical part of optimizing ADC design and delivery i.e., dose and schedule. This review discusses the pharmacokinetic considerations for an ADC and tools and strategies that can be used to evaluate molecules at the preclinical stage.

摘要

抗体药物偶联物(ADCs)是一类新兴的癌症靶向治疗药物,它利用抗体将细胞毒性药物递送至癌细胞。目前市场上有两种获美国食品药品监督管理局(FDA)批准的ADCs,临床研发管线中有30多种ADCs,针对多种不同类型的癌症。ADCs的结构非常复杂,包含多个组分,目前正在付出巨大努力来确定实现临床成功所必需的属性。了解ADCs的药代动力学及其对疗效和毒性的影响,是优化ADCs设计与给药(即剂量和给药方案)的关键部分。本综述讨论了ADCs的药代动力学考量以及可用于临床前阶段评估分子的工具和策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0643/4596897/79ad08c3e1bb/11095_2014_1584_Fig1_HTML.jpg

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