In vitro models are indispensable in drug development to prioritize new chemical entities, and to estimate the pharmacokinetic parameters in humans that are integrated into the pharmacokinetic models to predict in vivo pharmacokinetic profiles of the new chemical entities. Various in vitro models have been developed for drug development. Recently, we introduced the technique to differentiate the absorption epithelial cells from human jejunal spheroids. The epithelial cells showed the CYP3A4 activities that could reasonably account for in vivo availability of CYP3A4 substrates. Furthermore, they also maintain the transport activities which are well characterized in the intestine. The model will be useful to investigate the drug absorption, and therapeutic and toxic effects of drugs on the intestinal epithelial cells in humans. We can successfully prepare the spheroids from various regions of the intestine to investigate regional dependence of the drug absorption. Microphysiologic system (MPS) is an emerging in vitro experimental system. MPS include a co-culture system, microfluidics, and etc. to mimic the physiological conditions in vitro. We are trying to establish the intestine models using microfluidics.
Michiba K et al., Drug Metab Dispos, 50:204-213, 2022