title: Application of Pharmacokinetic-Pharmacodynamic Modeling and Simulation for Antibody-Drug Conjugate Development.
abstract: Characterization and prediction of the pharmacokinetics (PK) and pharmacodynamics (PD) of Antibody-Drug Conjugates (ADCs) is challenging, since it requires simultaneous quantitative understanding about the PK-PD properties of three different molecular species i.e., the monoclonal antibody, the drug, and the conjugate. Mathematical modeling and simulation provides an excellent tool to overcome these challenges, as it can simultaneously integrate the PK-PD of ADCs and their components in a quantitative manner. Additionally, the computational PK-PD models can also serve as a cornerstone for the model-based drug development and preclinical-to-clinical translation of ADCs. To provide an overview of this subject matter, this manuscript reviews the PK-PD models applicable to ADCs. Additionally, the usage of these models during different drug development stages (i.e., discovery, preclinical development, and clinical development) is also emphasized. The importance of PK-PD modeling and simulation in making rationale go/no-go decisions throughout the drug development process is also highlighted. There is an array of PK-PD models available, ranging from the systems models specifically developed for ADCs to the empirical models applicable to all chemotherapeutic agents, which one can employ for ADCs. The decision about which model to choose depends on the questions to be answered, time at hand, and resources available.
authors: Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, The State University of New York at Buffalo, 455 Kapoor Hall, Buffalo, New York, 14214-8033, USA.
authors: Aman P
authors: AP
authors: Singh
authors: College of Pharmacy, Chungnam National University, Daejeon, South Korea.
authors: Young G
authors: YG
authors: Shin
authors: Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, The State University of New York at Buffalo, 455 Kapoor Hall, Buffalo, New York, 14214-8033, USA. dshah4@buffalo.edu.
authors: Dhaval K
authors: DK
authors: Shah
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D003198:Computer Simulation; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008954:Models, Biological; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D018796:Immunoconjugates
keywords: PK-PD; antibody-drug conjugate (ADC); model based drug development; modeling and simulation; pharmacodynamics; pharmacokinetics; preclinical-to-clinical translation