药物开发
双特异性抗体
机制(生物学)
药品
计算生物学
医学
药效学
药物发现
计算机科学
药代动力学
药理学
抗体
生物信息学
免疫学
生物
单克隆抗体
认识论
哲学
作者
Jin Niu,Weirong Wang,Danièle Ouellet
标识
DOI:10.1080/17512433.2023.2257136
摘要
Unlike conventional antibodies, bispecific antibodies (bsAbs) are engineered antibody- or antibody fragment-based molecules that can simultaneously recognize two different epitopes or antigens. Over the past decade, there has been an explosion of bsAbs being developed across therapeutic areas. Development of bsAbs presents unique challenges and mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) modeling has served as a powerful tool to optimize their development and realize their clinical utility.In this review, the guiding principles and case examples of how fit-for-purpose, mechanism-based PK/PD models have been applied to answer questions commonly encountered in bsAb development are presented. Such models characterize the key pharmacological elements of bsAbs, and they can be utilized for model-informed drug development. We also include the discussion of challenges, knowledge gaps and future direction for such models.Mechanistic PK/PD modeling is a powerful tool to support the development of bsAbs. These models can be extrapolated to predict treatment outcomes based on mechanisms of action (MoA) and clinical observations to form positive learn-and-confirm cycles during drug development, due to their abilities to differentiate system- and drug-specific parameters. Meanwhile, the models should keep being adapted according to novel drug design and MoA, providing continuous opportunities for model-informed drug development.
科研通智能强力驱动
Strongly Powered by AbleSci AI