Components of the Ideal GIT Model

8 THE OPTIMIZED PAMPA MODEL FOR THE GUT 7.8.1 Components of the Ideal GIT Model 

The examination of over 50 PAMPA lipid models has led to an optimized model for gastrointestinal tract (GIT) absorption. Table 7.22 shows six properties of the GIT, which distinguish it from the blood-brain barrier (BBB) environment. 

The in vitro measurements of permeability by the cultured-cell or PAMPA model underestimate true membrane permeability, because of the UWL, which ranges in thickness from 1500 to 2500 pm. The corresponding in vivo value is 30-100 pm in the GIT and nil in the BBB (Table 7.22). The consequence of this is that highly permeable molecules are (aqueous) diffusion limited in the in vitro assays, whereas the membrane-limited permeation is operative in the in vivo case. Correcting the in vitro data for the UWL effect is important for both GIT and BBB absorption modeling. 

The in vivo environment of the GIT is characterized by a pH gradient the pH value is constant at 7.4 in the receiving compartment (blood), and varying in the donor compartment (lumen) from 5 to 8 from the start to the end of the small intestine. In contrast, the BBB has a constant iso-pH 7.4. Modeling the two environments requires proper pH adjustment in the in vitro model, as indicated in Table 7.22. 

The receiver compartment in the GIT has a strong sink condition, effected by serum proteins. In contrast, the BBB does not have a strong sink condition. In the GIT, lipophilic molecules are swept away from the site of absorption in 

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