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In vitro assessment of combination dosing regimen with in vivo-like pharmacokinetic concentration profiles enabled by a microfluidic addition and removal device
American Associate for Cancer Research (AACR)
Filed under: ADME, Disease modeling, and Oncology
Golby et al
The pharmacokinetic (PK) profile is a determining factor in both the safety and efficacy of a drug or therapeutic regimen. PK profiles can vary significantly between patients and between humans and pre-clinical animal species.
Mouse Xenograft models are ubiquitous in oncology research, widely utilized to study single agents, combinations, and scheduling. Differences in PK between mice and humans are one factor limiting the translational relevance of xenograft studies. Additionally, studies to assess combinations and/or scheduling quickly require large numbers of animals owing to the many possible permutations.
Here we describe a device capable of recapitulating PK-like profiles in vitro and explore the effects of PK on the treatment of non-small-cell lung carcinoma by erlotinib alone and in combination with pemetrexed.