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Investigating the PK/PD/efficacy relationship of PI3K inhibitors in vitro, enabled by a microfluidic addition and removal device
Filed under: ADME, Disease modeling, and Oncology
Singh et al
Characterizing the relationship between pharmacokinetics (PK), pharmacodynamics (PD), and efficacy is critical in the discovery and development of new drugs, schedules, and combinations. The PK/PD/efficacy relationship has historically been characterized in xenograft models, owing to an absence of viable alternatives. The study of this relationship in vitro has to date been problematic as the generation of time-varying concentrations in multi-well plates has not been possible.
Here, we have explored an in vitro methodology utilizing a device capable of recapitulating PK-like profiles in vitro. Through stepwise addition and removal of medium from the wells of a microtiter cell culture plate the device was able to recapitulate PK-like, time-varying concentration profiles of one, or more drugs in individual wells.