Correlation to Fraction of Oral Dose 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. 

As the Caco-2 cell model contains most of the important transporters, it can be used for the study not only of passive transport mechanisms but also of mechanisms involving transporters. This is a major advantage of the Caco-2 model when 

Another limitation of the Caco-2 monolayers is their colonic origin and tight paracellular pathway, which tend to lead to underestimations in permeability to paracellularly transported compounds [97]. This is likely to be correct for small compounds (MW 150) - i.e., compounds smaller than normal drugs - but it remains to be seen to what extent the Caco-2 model gives false-negative predictions of the fraction absorbed for polar drugs of normal size in humans where para- 

Ranitidine 61 Moderate 9 Fa calculated from Fa — F/(l — CLh/Qh). Interaction with transporters 

Digoxin 81 High 10 Fa calculated from urinary exretion data of p.o. and i.v. administered P-gp substrate 

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