Abstract
The increased development and availability of therapeutic proteins (TP) requires a greater understanding of drug-drug interactions (DDI) in a poly-pharmacy environment. Medications that are likely co-administered in various patient populations have to be considered in the context of direct pharmacokinetic properties of co-administered drugs as well as indirect effects due to disease modification. Anticipating and managing drug-drug interactions are an important part of the clinical development of both small and large molecules. Animal models may provide useful information in this regard with respect to human translatability. However, very limited work has been done to better understand the value of animal models for predicting the potential for TP DDI. Potential DDI mechanisms of TPs, with the exception of cytokine-mediated alteration of drug metabolizing enzymes and transporters, are less well known. This review discusses the potential value and specific challenges in the use of animal models for TP DDI evaluation.
Keywords: Animal, biotherapeutic, drug-drug interaction, Models, Interaction, pathophysiology, clinical DDI, Ab-receptor, drug metabolizing enzymes, metabolizing enzyme, translation.
Current Drug Metabolism
Title:Animal Models for Evaluation of Drug-Drug Interaction Potential of Biotherapeutics
Volume: 13 Issue: 7
Author(s): Eugenia Kraynov, Martin E. Dowty, Odette Odette A. Fahmi and Owen Fields
Affiliation:
Keywords: Animal, biotherapeutic, drug-drug interaction, Models, Interaction, pathophysiology, clinical DDI, Ab-receptor, drug metabolizing enzymes, metabolizing enzyme, translation.
Abstract: The increased development and availability of therapeutic proteins (TP) requires a greater understanding of drug-drug interactions (DDI) in a poly-pharmacy environment. Medications that are likely co-administered in various patient populations have to be considered in the context of direct pharmacokinetic properties of co-administered drugs as well as indirect effects due to disease modification. Anticipating and managing drug-drug interactions are an important part of the clinical development of both small and large molecules. Animal models may provide useful information in this regard with respect to human translatability. However, very limited work has been done to better understand the value of animal models for predicting the potential for TP DDI. Potential DDI mechanisms of TPs, with the exception of cytokine-mediated alteration of drug metabolizing enzymes and transporters, are less well known. This review discusses the potential value and specific challenges in the use of animal models for TP DDI evaluation.
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Kraynov Eugenia, E. Dowty Martin, Odette A. Fahmi Odette and Fields Owen, Animal Models for Evaluation of Drug-Drug Interaction Potential of Biotherapeutics, Current Drug Metabolism 2012; 13 (7) . https://dx.doi.org/10.2174/138920012802138705
DOI https://dx.doi.org/10.2174/138920012802138705 |
Print ISSN 1389-2002 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5453 |
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