Cultures for Assessment of Intestinal Permeability

Predicted octanol/water partitioning coefficient Fraction of the oral dose absorbed Apparent permeability coefficient 

Caco-2 cells form tight junctions and express many of the brush border enzymes (hydrolases) that are found in the normal small intestine, for example, alkaline phosphatase, sucrase, and amino peptidases [26-29]. Cytochrome P450 (CYP450) isoenzymes and some phase II enzymes (e.g., glutathione-S-transferases, sulfotrans-ferase, and glucuronidase) have been identified [29-33] in these cells however, the level of CYP expression (e.g., CYP3A4) is low in the original cells under standard cell culture conditions [34]. 

In general, the inherent expression of canine transport proteins in MDCK cells is low. This fact together with the seemingly correct sorting of transport proteins to the right location in the plasma membrane has made these cells a popular choice for the 

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The introduction of new technologies in recent years is increasing the throughput of ADME studies during the drug discovery process. The advent of cell culture techniques in recent years has facilitated the assessment of intestinal permeability for many drugs. A notable example is the use of CaCO-2 cells, an immortalized human colon adenocarcinoma cell line... 

The identification and characterization of cell culture systems (e.g., Caco-2-cells) that mimic in vivo biological barriers (e.g., intestinal mucosa) have afforded pharmaceutical scientists the opportunity to rapidly and efficiently assess the permeability of drugs through these barriers in vitro. The results generated from these types of in vitro studies are generally expressed as effective permeability coefficients (Pe). If Pe is properly corrected to account for the barrier effects of the filter (PF) and the aqueous boundary layer (PAbl) as previously described in Section II.C, the results provide the permeability coefficient for the cell monolayer... 

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