文章：

抗体-药物偶联物的药代动力学与药效学建模

Pharmacokinetic and Pharmacodynamic Modeling of Antibody-Drug Conjugates

原文发布日期：19 December 2025

DOI: 10.3390/cancers18010005

类型: Article

开放获取: 是

英文摘要：

Antibody-drug conjugates (ADCs) have risen in prominence over the past 15 years, with numerous regulatory approvals in oncology. A complicating factor in the development of ADCs is the presence of numerous analytes with unique pharmacologic properties. Following administration, ADCs are present in the body as the intact ADC, unconjugated antibody, and liberated payload. Due to heterogeneity in conjugation and in vivo deconjugation rates, the drug-to-antibody ratio (DAR) changes with time. Each of these molecular species has unique pharmacokinetic (PK) and pharmacodynamic (PD) properties that should be understood and characterized. One approach that is frequently applied is the development of in silico mathematical models to characterize and predict the PK/PD of ADCs. In this review, we summarize key mechanisms controlling the PK/PD of ADCs. This provides context for a detailed discussion of the array of PK/PD models that have been applied for ADCs, ranging from empirical compartmental models all the way through system-level models, such as physiologically based pharmacokinetics (PBPK) and cell-level PK/PD models. We provide a critical discussion of the strengths, weaknesses, and utility of each of these model structures.

摘要翻译： 

抗体药物偶联物（ADC）在过去15年中日益受到重视，并在肿瘤治疗领域获得多项监管批准。ADC研发过程中的一个复杂因素在于存在多种具有独特药理特性的分析物。给药后，ADC在体内以完整偶联物、未偶联抗体及游离载荷药物三种形式存在。由于偶联过程的异质性和体内解偶联速率差异，药物抗体比率（DAR）会随时间动态变化。这些分子形式均具有独特的药代动力学（PK）和药效学（PD）特性，需要深入理解和表征。目前常采用的计算建模方法是通过计算机数学模型来表征和预测ADC的PK/PD特性。本综述系统阐述了调控ADC药代/药效的关键机制，在此基础上详细探讨了应用于ADC的各类PK/PD模型——从经验性房室模型到系统层面模型（如基于生理的药代动力学模型PBPK）及细胞层面PK/PD模型，并对各类模型结构的优势、局限及应用价值进行了批判性评述。

原文链接：

Pharmacokinetic and Pharmacodynamic Modeling of Antibody-Drug Conjugates