Figure 7.63 Human jejunal permeabilities compared to pION's double-sink sum-Pe PAMPA GIT model.

UWL), and the data represented by the dashed line corresponds to Pe values (uncorrected for the UWL, r2 data not shown in Table 7.23).

The pION double-sink GIT model, with donor pH 5, predicts the human jejunal permeabilities as well as the best reported Caco-2 model (Artursson's), and a lot better than the rest of the reported Caco-2 models, as shown in Fig. 7.63.

7.8.4 Caco-2 Models for Prediction of Human Intestinal Absorption (HIA)

The strategy of the preceding sections was based on predicting the permeabilities of drug compounds in the human jejunum. The rest of the intestinal tract has higher pH, and this needs to be factored in when considering models to predict not human permeabilities, but human absorption (see Fig. 2.3 and Table 7.2).

Caco-2 permeabilities have been used to predict human intestinal absorption (HIA) in the literature. Figure 7.64 is a plot of %HIA versus log PeCaco-2, drawing on the published work of about a dozen laboratories. The plot in Fig. 7.64 resembles ''rain,'' and perhaps very little can be learned from such a plot. This may be an example of what Lipinski [1] pointed out as the consequences of using multimecha-nistic ADME measurements—the more data points are brought in, the worse the plot looks. Another way of looking at this is that each laboratory has a somewhat differently expressed Caco-2 line, and interlaboratory comparisons can only be done in a rank-order sense. When individual-laboratory data are examined, some groups have better correlations than others. Figure 7.65 shows the results from

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