Permeability in vivo

The experimental Pjpp data have been used to build predictive models. However, since PAMPA is already a model, an in silica model based on this is a model of a model. The predictability for in vivo permeability or absorption of such in silica PAMPA model can be queshoned (see Eq. 11), since it is two steps from reality ... 

The transport properties of the molecules in concentrated soy lecithin (see Table 3.3) do not adequately model the in vivo permeabilities reported by Winiwarter et al. [36] (see Table 3.6). The strategy to overcome this shortcoming involves creating a significant sink condition in the acceptor wells. However, the... 

In vivo Permeability Studies in the Gastrointestinal Tract of Humans... 

Fig. 7.6. a-c. Human in vivo permeabilities (Loc-I-Gut ) (see Fig. 7.4). The major are a cornerstone of the BCS the correlation of advantage of using Peff is that it can be fraction dose absorbed and permeability with measured irrespective of transport mecha-...

Fig. 7.7. Human in vivo permeability values (Peff) can be determined using a single-pass perfusion technique (Loc-I-Gut) in humans. These human Peff values correlated very well...

Fig. 7.16. Ketoconazole had no effect on human effective in vivo permeability (Pefr) of R/S-verapamil, antipyrine, and D-glucose. The data suggest that extensive intracellular metabolism (in the enterocyte mediated by CYP 3A4) of substrates such as R/S-verapamil...

A residence-time distribution analysis of the hydrodynamics within the intestine in man during a regional single-pass perfusion with Loc-I-Gut in-vivo permeability estimation, J. Pharm. Pharmacol. 1997, 49, 682-686. 

Predictions of human in vivo permeability can be made with a particularly high degree of accuracy in all predinical models for drugs with passive diffusion as their main mechanism. It is only the dog model that seems to absorb low-permeability... 

Lennernas H, Lee I, Fagerholm U and Amidon GL (1997) A Residence-Time Distribution Analysis of the Hydrodynamics Within the Intestine in Man During a Regional Single-Pass Perfusion With Loc-I-Gut In-Vivo Permeability Estimation. J Pharm Pharmacol 49 pp 682-686. 

Despite the availability of other cell lines, Caco-2 cells remain the most widely used intestinal cell culture model at present. This model has provided valuable information necessary for lead optimization in the drug discovery process. However, it is important to understand that compounds with high permeability in this model are typically well absorbed, whereas compounds with low solubility and low permeability in this model may not necessarily be poorly absorbed in vivo. Although this type of positive selection limits the usefulness in providing a structure-permeability relationship, the Caco-2 model has the most effect in drug discovery when the screen is implemented early and in conjunction with other types of in vitro and in vivo permeability/absorption screens. 

To predict in vivo permeabilities, the parallel artificial membrane permeability assay (PAMPA) was introduced in 1998. Since then, it has gathered considerable interest in the pharmaceutical industry [41-47]. This method uses a phospholipid-coated filter separating two aqueous compartments to mimic the passive transport of small molecules. It readily provides information about passive-transport perme-... 

Table 1 In vitro Papp (cm/sec) values corresponding to 20 % and 80 % in vivo permeability data from sigmoidal correlation curve with standard compounds.

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