The quest for balance between capturing data and model complexity: A quantitative clinical pharmacology approach applied to monoclonal antibodies
CPT Pharmacometrics & Systems Pharmacology, vol. 12, pp. 639–655
Abstract
The main objective of this tutorial is to provide the readers with a roadmap of how to establish increasingly complex target-mediated drug disposition (TMDD) models for monoclonal antibodies. To this end, we built mathematical models, each with a detailed visualization, starting from the basic TMDD model by Mager and Jusko to the well-established, physiologically based model by Li et al. in a step-wise fashion to highlight the relative importance of key physiological processes that impact mAb kinetics and system dynamics. As the models become more complex, the question of structural and parameter identifiability arises. To address this question, we work through a trastuzumab case example to guide the modeler's choice for model and parameter optimization in light of the context of use. We leave the readers of this tutorial with a brief summary of the advantages and limitations of each model expansion, as well as the model source codes for further self-guided exploration and hands-on analysis.
Authors 8
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Affiliation as printed
Department of Pharmaceutics, College of Pharmacy, Center for Pharmacometrics and System Pharmacology at Lake Nona (Orlando) University of Florida Gainesville Florida USA
Department of Pharmaceutics, College of Pharmacy, Center for Pharmacometrics and System Pharmacology at Lake Nona (Orlando), University of Florida, Gainesville, Florida, USA
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Affiliation as printed
Mathematical Institute Leiden University Leiden The Netherlands
Mathematical Institute, Leiden University, Leiden, The Netherlands
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Janssen Research & Development (United States)
Affiliation as printed
Adagene, Inc. San Diego California USA
Biologics Clinical Pharmacology Janssen R&D Spring House Pennsylvania USA
Adagene, Inc., San Diego, California, USA
Biologics Clinical Pharmacology, Janssen R&D, Spring House, Pennsylvania, USA
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Affiliation as printed
Department of Pharmaceutics, College of Pharmacy, Center for Pharmacometrics and System Pharmacology at Lake Nona (Orlando) University of Florida Gainesville Florida USA
Department of Pharmaceutics, College of Pharmacy, Center for Pharmacometrics and System Pharmacology at Lake Nona (Orlando), University of Florida, Gainesville, Florida, USA
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Genentech · University of Florida
Affiliation as printed
Clinical Pharmacology Genentech Research and Early Development South San Francisco California USA
Department of Pharmaceutics, College of Pharmacy, Center for Pharmacometrics and System Pharmacology at Lake Nona (Orlando) University of Florida Gainesville Florida USA
Clinical Pharmacology, Genentech Research and Early Development, South San Francisco, California, USA
Department of Pharmaceutics, College of Pharmacy, Center for Pharmacometrics and System Pharmacology at Lake Nona (Orlando), University of Florida, Gainesville, Florida, USA
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Janssen Research & Development (United States)
Affiliation as printed
Biologics Clinical Pharmacology Janssen R&D Spring House Pennsylvania USA
Biologics Clinical Pharmacology, Janssen R&D, Spring House, Pennsylvania, USA
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Janssen Research & Development (United States)
Affiliation as printed
Biologics Clinical Pharmacology Janssen R&D Spring House Pennsylvania USA
Kira Pharmaceuticals Cambridge Maryland USA
Biologics Clinical Pharmacology, Janssen R&D, Spring House, Pennsylvania, USA
Kira Pharmaceuticals, Cambridge, Maryland, USA
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Stephan Schmidt corresponding
Affiliation as printed
Department of Pharmaceutics, College of Pharmacy, Center for Pharmacometrics and System Pharmacology at Lake Nona (Orlando) University of Florida Gainesville Florida USA
Department of Pharmaceutics, College of Pharmacy, Center for Pharmacometrics and System Pharmacology at Lake Nona (Orlando), University of Florida, Gainesville, Florida, USA
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