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 P(app) 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 P(app) 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.