TABLE 4

A comparison of the various in vitro experimental systems in their applications, strengths, and limitations for the evaluation of enteric drug properties

Model classification	Experimental systems	Applications							Strengths	Limitations
Model classification	Experimental systems	Permeability	Uptake transport	Efflux transport	Drug metabolism	Metabolic DDI	Transporter DDI	Enterotoxicity	Strengths	Limitations
Cell lines	Caco-2	Yes	Yes	Yes (P-gp)	No	No	Yes	Limited due to incomplete drug metabolism enzyme pathways	Extensive database; applied extensively in BCS drug characterization; expression of uptake and efflux transporters	Requires prolonged culturing (14 days) for establishment of barrier characteristics
Cell lines	Caco-2	Yes	Yes	Yes (P-gp)	No	No	Yes	Limited due to incomplete drug metabolism enzyme pathways		Lacks drug metabolizing enzymes
Crypt cell/iPSC–derived models	Enteroids	Possible	Possible	Yes	No	No	Possible	Limited due to incomplete drug metabolism enzyme pathways	Human enteric cells appropriate for the elucidation of enteric differentiation	Lacks drug metabolizing enzyme activities
Crypt cell/iPSC–derived models	Monolayer cultures	Possible	Possible	Yes	No	No	Possible	Limited due to incomplete drug metabolism enzyme pathways		Lacks drug metabolizing enzyme activities
Primary cell/organ models	Intestinal slices	Possible	Possible	Possible	Yes	Yes	Possible	Yes	Complete enteric drug metabolizing enzyme activities	Requires slice preparation on day of experimentation
	Cryopreserved enterocytes	Possible	Possible	Possible	Yes	Yes	Possible	Yes	Complete enteric drug metabolizing enzyme activities	Relatively low drug metabolizing enzyme activities compared with MetMax enterocytes and CHIM
	MetMax enterocytes	Possible	No	No	Yes	Yes	No	Yes	Complete enteric drug metabolizing enzyme activities; simple use procedures	Cannot be used for transport studies due to permeabilized plasma membranes (but can be used in conjuction with intact enterocytes to delineate role of permeability on experimental endpoints)
	Cryopreserved intestinal mucosa	Possible	Possible	Possible	Yes	Yes	Possible	Yes	Complete enteric drug metabolizing enzyme activities; complete mucosa allowing experimentation with all mucosal cell types	Approaches for uptake and efflux transport, though theoretically feasible, have not yet been developed

DDI, drug-drug interactionBCS, biopharmaceutics classification system