A possibility to predict the absorbability of poorly water-soluble drugs in humans based on rat intestinal permeability assessed by an in vitro chamber method

This paper describes a means to predict the absorbability of poorly water-soluble drugs in humans based on rat intestinal permeability assessed by the in vitro Ussing-type chamber method. We investigated the correlation between the apparent permeability coefficients (P-app) of 10 water-soluble drugs obtained by the in vitro chamber method, in which the excised rat small intestinal tissue was used as the membrane, and the fractions absorbed (F-a) in humans. Using this correlation, we predicted F-a values of 5 poorly water-soluble drugs based on their Papp obtained through our modified chamber method using an additive. For water-soluble drugs, a good correlation between P-app and F-a, expressed by the equation: F-a = 1 - exp(-P-app X 1.51 X 10(5))(r(2) = 0.920), was found. The poorly water-soluble drugs used in the present study could be solubilized with 5% (final concentration) dimethylsulfoxide, and their Papp could be obtained through our modified chamber method. For poorly water-soluble drugs whose dose:solubility ratio ranged from 2500 to 3500 ml, predicted F-a values were favorably comparable with their F-a values reported in humans in the literature. These results showed that the in vitro Ussing-type chamber method was a useful method for predicting the F-a of poorly water-soluble drugs. (C) 2004 Elsevier B.V. All rights reserved.