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Abstract

The in vitro permeabilities of Caco-2 monolayers and permeabilities in tissue sections from colon of monkey, rabbit, and dog were compared using a series of compounds. The selected compounds differed in their physicochemical properties, such as octanol/water partition coefficient, water solubility, and molecular weight. Their structure included steroids, carboxylic acids, xanthins, alcohols, and polyethylene glycols. A linear permeability relationship was established between Caco-2 and colon tissue from both rabbit and monkey. The results suggest that Caco-2 is twice as permeable as rabbit and five times as permeable as monkey colon. However, no clear relationship could be established between Caco-2 monolayers and dog colon permeability. A relationship between permeability in Caco-2 monolayers and human absorption was found. The results suggest that within certain limits, permeability of Caco-2 monolayers may be used as a predictive tool to estimate human drug absorption.

Assessment and modulation of phillyrin absorption by P-gp using Caco-2 cells and MDR1-MDCKII cells

“…The absorptive P app were estimated to be 7.15, 6.39, 10.03 9 10 -6 cm s -1 , respectively, for different concentrations, which were well below the suggested threshold value (1.0 9 10 -5 cm s -1 ) for poorly absorbed compounds (Rubas et al 1993) and consistent with the low oral bioavailability of phillyrin observed in pharmacokinetic experiments. In contrast to absorptive transport, the secretory transport appeared to be concentration-dependent suggesting the involvement of a transporter or multiple transporters.…”

Modified low molecular weight cyclic peptides as mimetics of BDNF with improved potency, proteolytic stability and transmembrane passage in vitro

“…Despite this, relating P app in this assay for a given compound to its likely in vivo absorption remains a difficult prospect. Several groups [29][30][31][32] have reported very strong individual correlations between P app across Caco-2 monolayers and in vivo absorption across intestinal epithelium in vivo. However, as noted by Artursson and colleagues 33 the correlation between studies is poor.…”

In vitro systems for studying intestinal drug absorption

“…Active transport is more difficult in that it needs to be evaluated separately for each transporter studied. 189 are about an order of magnitude greater. This is most likely due to the fact that Rubas et al 189 used a system in which the unstirred water layer was reduced while Artursson and Karlsson188 used a stagnant system.…”

“…189 are about an order of magnitude greater. This is most likely due to the fact that Rubas et al 189 used a system in which the unstirred water layer was reduced while Artursson and Karlsson188 used a stagnant system. Completely absorbed drugs in humans had Papp values greater than 1 x 10-6 cm/s and 7 x 10-5 cm/s in Artursson's and Rubas' models, respectively.…”