Modeling Pharmacokinetics and Pharmacodynamics of Therapeutic Antibodies: Progress, Challenges, and Future Directions

被引：23

作者：

Tang, Yu ^{[1
]}

Cao, Yanguang ^{[1
,2
]}

机构：

[1] Univ North Carolina Chapel Hill, UNC Eshelman Sch Pharm, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC 27599 USA

[2] Univ North Carolina Chapel Hill, Lineberger Comprehens Canc Ctr, Sch Med, Chapel Hill, NC 27599 USA

来源：

PHARMACEUTICS | 2021年 / 13卷 / 03期

基金：

美国国家卫生研究院;

关键词：

therapeutic antibody; PK; PD modeling; recycling antibody; bispecific antibody; tissue distribution; target engagement; effector functions; resistance; BLOOD-BRAIN-BARRIER; RESONANCE ENERGY-TRANSFER; ANTITRANSFERRIN RECEPTOR ANTIBODY; DEPENDENT ANTIGEN-BINDING; NEONATAL FC-RECEPTOR; CHRONIC LYMPHOCYTIC-LEUKEMIA; LINKED-IMMUNOSORBENT-ASSAY; IMMUNE-CHECKPOINT BLOCKADE; MEDIATED DRUG DISPOSITION; HUMAN MONOCLONAL-ANTIBODY;

D O I：

10.3390/pharmaceutics13030422

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

With more than 90 approved drugs by 2020, therapeutic antibodies have played a central role in shifting the treatment landscape of many diseases, including autoimmune disorders and cancers. While showing many therapeutic advantages such as long half-life and highly selective actions, therapeutic antibodies still face many outstanding issues associated with their pharmacokinetics (PK) and pharmacodynamics (PD), including high variabilities, low tissue distributions, poorly-defined PK/PD characteristics for novel antibody formats, and high rates of treatment resistance. We have witnessed many successful cases applying PK/PD modeling to answer critical questions in therapeutic antibodies' development and regulations. These models have yielded substantial insights into antibody PK/PD properties. This review summarized the progress, challenges, and future directions in modeling antibody PK/PD and highlighted the potential of applying mechanistic models addressing the development questions.

引用

页数：28