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抗体药物偶联物(ADC)是由具有靶向特异性的单抗和具有高毒性的小分子结合而成的新药,与单抗和小分子药物相比,具有特异性高和毒性低的特征。由于这种特性,用于ADC的药动学(PK)研究的生物分析方法的建立和选择具有挑战性。同时大分子抗体和小分子组分的药物,生物分析方法的组合对了解ADC的体外与体内过程,认识药物运送到作用部位和暴露反应关系十分重要。因此,对ADC的开发策略、新生物分析方法的开发、建立和验证,以及临床前和临床PK、PK/PD研究的问题的挑战和机遇必须有足够认识。就ADC的药动学研究的进展和难点予以介绍,以期与从事该类药物的研究者一起讨论和分析。
Antibody drug conjugates (ADCs) are new drugs that combine targeting-specific monoclonal antibodies with small, highly toxic molecules that are characterized by high specificity and low toxicity compared to monoclonal antibodies and small molecule drugs . Due to this property, the establishment and selection of bioanalysis methods for pharmacokinetic (PK) studies of ADCs are challenging. At the same time, the combination of macromolecular antibodies and small molecule drug and bioanalysis methods is very important to understand the process of ADC in vitro and in vivo, and to understand the relationship between drug delivery to the site of action and exposure. Therefore, there is a need to be aware of the development strategies of ADCs, the development, establishment and validation of new bioanalytical methods, as well as the challenges and opportunities of the preclinical and clinical PK and PK / PD research questions. On the progress of the pharmacokinetics of ADC and the difficulties are introduced, with the researchers engaged in such drugs to discuss and analyze.