抗体偶联药物吸收、分布、代谢、排泄和毒性特征及分析方法研究进展

Absorption,distribution,metabolism,excretion and toxicity of antibody-drug conjugates and its research progress on analytical approaches

抗体偶联药物(antibody-drug conjugate,ADC)将单克隆抗体药物的高特异性和小分子细胞毒药物的高活性相结合,用以提高肿瘤药物的靶向性、减少毒副作用。由于ADC分子的结构特异性,其药动学特征(pharmacokinetic,PK)、毒理学机制及生物分析方法与单纯的大分子或小分子药物相比,更具复杂性和多样性,使其研发和临床试验面临巨大的挑战。本文就ADC在体内的吸收(absorption)、分布(distribution)、代谢(metabolism)、排泄(excretion)和毒性(toxicity)特征,以及ADC药物在研发过程中常见的生物分析方法研究策略等方面进行阐述。

Antibody-drug conjugate(ADC)composes the high specificity of monoclonal antibody and the high activity of small cytotoxic moieties through a chemical linker and can improve the targeted antitumor drug delivery with minimizing the systemic toxicity.The pharmacokinetic characteristics,toxicology mechanism and analytical methods of ADC are more complex and diverse than those of antibodies or small molecular drugs because of the structural specificity of ADC molecules,which makes the research,development and clinical trials of ADC face great challenges.This paper reviews the characterization of ADMET(absorption,distribution,metabolism,excretion and toxicology)and common biological analysis methods and research strategies in the research and development process of ADC.