抗体药物偶联物药动学研究进展  

Advances in Research on Pharmacokinetics of Antibody-drug Conjugates

作　　者：于丝雨 刘晓东[1] 刘李[1] YU Siyu;LIU Xiaodong;LIU Li(Center of Drug Metabolism and Pharmacokinetics,School of Pharmacy,China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]中国药科大学药学院药物代谢研究中心,江苏南京211198

出　　处：《药学进展》2021年第3期188-195,共8页Progress in Pharmaceutical Sciences

摘　　要：抗体药物偶联物是临床上用于治疗多种恶性肿瘤的一种新型药物,其由单克隆抗体、细胞毒性小分子药物、抗体-药物连接子这3个部分构成。尽管抗体药物偶联物同时具有单克隆抗体的高靶向特异性和细胞毒性小分子药物的强细胞毒性,许多抗体药物偶联物在临床试验阶段仍因毒副作用大、有效性低等问题而被宣告失败。体内药动学分析和预测可为抗体药物偶联物的分子设计与给药方案确定提供重要参考。总结了影响抗体药物偶联物体内药动学的多方面因素以及体内药动学的常用生物分析手段,并为抗体药物偶联物的体内药动学和药效学的合理预测提供了理论参考。Antibody-drug conjugates(ADCs)are a new class of therapeutic drugs for the treatment of many different malignant tumors.An ADC consists of a monoclonal antibody,a potent cytotoxic small molecule chemotherapeutic(payload)and a chemical linker.Although ADC has both high target specificity of the antibody and highly potential cytotoxicity of the payload,many failed amid the clinical trials because of the high toxicity or low efficacy.In this case,the analysis of pharmacokinetic properties and predication of ADCs in vivo can provide significant reference for the structural design of ADCs and the determination of dosing regimens.This review summarizes multifaceted factors for the pharmacokinetics of ADCs and the commonly used bioanalytical tools of ADCs pharmacokinetics,and provides theoretical reference for the reasonable predication of pharmacokinetics and pharmacodynamics of ADCs in vivo.

关 键 词：抗体药物偶联物 药动学 生物分析 药动学-药效学模型 

分 类 号：R979.1[医药卫生—药品] R969.1[医药卫生—药学]