In Vitro Modeling of Drug-Drug Interactions
In vitro modeling of drug-drug interactions (DDI) has tremendous potential to impact the prediction and management of DDIs during the development of new anti-infective agents positively. In this chapter, two fundamental types of in vitro models used for predicting and managing DDIs are introduced and discussed. The first type, referred to as static DDI models, produces a steady-state prediction of compound exposure change upon coadministration with a perpetrator of DDI. The second type of in vitro DDI model, the physiologically based pharmacokinetic (PBPK) model, combines in vitro data with a physiological representation of organs and blood flows and can provide a dynamic prediction of more complex DDI involving transporter/enzyme interplay and the effect of disease pathophysiology. The science of in vitro-in vivo extrapolation (IVIVE) for transporters, transporter/enzyme interplay, and special populations/diseases is currently developing at a rapid pace; however, in vitro modeling of DDI is already a scientifically mature subject with increasing regulatory acceptance and is evolving into a key asset to help in the development of life-altering medicines for patients in need.
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