Animal Models for Evaluation of Drug-Drug Interaction Potential of Biotherapeutics

Eugenia      Kraynov; Martin      E. Dowty; Odette      Odette A. Fahmi; Owen      Fields

doi:10.2174/138920012802138705

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.