Caco-2 cells correlation between fraction absorbed

Many academic and industrial laboratories have shown that the drug permeability measured in Caco-2 cell monolayers can be used to predict the oral absorption of drugs in humans. Various datasets have therefore been used to establish correlations between Caco-2 permeability and the fraction absorbed orally in humans [85, 86, 96]. Taken together, these studies show good predictability, though with a relatively wide variation in the appearance of correlation profiles between different laboratories [86]. These studies emphasize the need to establish correlations and standardization procedures in each laboratory. 

Figure 3 Correlation between the fraction absorbed and the membrane permeability in Caco-2 cells. Papp represents the membrane permeability of following 20 compounds, and was obtained by measuring the transcellular transport from the apical-to-basal side in Caco-2 cells. The fraction absorbed was obtained from literature. A amoxicillin, B antipyrine, C atenolol, D caffein, E cephalexin, F cyclosporin A, G enalaprilate, H L-glutamine, I hydrocortisone, J inulin, K D-mannitol, L metoprolol, M L-phenylalanine, N PEG-400, O PEG-4000, P propranolol, Q sucrose, R taurocholate, S terbutaline, T testosterone. Source From Ref. 37.

Some of the advantages of cell monolayer models include the ability to use human instead of animal cell types as well as the ability to perform cellular uptake and bidirectional cell transport studies for evaluation of absorptive and secretory processes. The potential for automation to achieve higher throughput in the early drug discovery setting is an added attraction. Regardless of the cell type used, the utility of these models in transport studies is based on the correlation between permeability properties determined in these models and those obtained in vivo, such as fraction of dose absorbed (Fig. 3). To date, numerous laboratories have established a correlation between apparent permeability coefficients (P pf) from Caco-2 or MDCK cells and in vivo fraction absorbed of drugs in solution [58—62]. Construction of correlation plots for known compounds or reference markers then provides an opportunity for interpolation of fraction absorbed for NMEs for which in vivo fraction absorbed is unknown. 

Excellent correlation for permeability coefficient between MDCK and Caco-2 cells was observed for 55 compounds with known human intestinal absorption. Regardless of the type of cells used in determining permeability measurement, establishing the correlation between the permeability coefficient and the fraction of drug absorbed in vivo validates this approach. 

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