Observations from Permeability Measurements

The most recent example of in silico efflux modeling has been based on Caco-2 permeability measured in the basal to apical direction [100]. This model can be very effective at ruling out compounds that most likely will show low in vivo intestinal absorption - however it carmot indicate which efflux pump(s) is/are responsible for that, making it more difficult for designers to circumvent the problem. Johnson [92] also included in his review an excellent summary of QSAR models and rules of thumb developed for P-gp substrates and inhibitors. These models are normally based on efflux ratios from MDCK/MDRl or Caco-2 cell lines - in the latter case it is important to notice that the data is combined with inhibition values from the calcein-AM assay, as the observed efflux might not be exclusively due to P-gp. 

Permeable Cell Assay for high-throughput measurement of cellular ATP synthetic activity (4). In this assay, osmotic shock and Triton X-100 treatment made bacterial cells permeable for ATP Discharged ATP reacted with external luciferase and is detected as bioluminescence. An increased bioluminescence is observed with permeable cells, whereas it is not observed with standard ATP solution and heat-inactivated permeable cells. The cellular ATP synthetic activity is calculated from the slope of increasing bioluminescence. Permeable Cell Assay is simple and rapid with a small amount of cell culmre for quantification of ATP synthesis. 

Permeabilities in shales have been calculated based on observed pressure gradients and fluid fluxes derived from compaction rates. At constant rates of subsidence the compaction-driven flux would be nearly constant over a limited section, thus the pressure gradients is inversely proportional to the permeability. Assuming a flux of 10" mVm per s, an effective permeability of about 1 nD was calculated, based on the observed pressure gradients. This is in good agreement with the permeabilities measured on samples (Schlbmer, 1995). 

Figure 15.1 shows the parameters pertinent to a field pumping test for permeability determination. One test well is required, and two observation wells are needed, both within the drawdown curve and at different radial distances from the test well. The test well is pumped at some constant rate until equilibrium elevations are attained in the observation wells. Field measurements of Q, ri, r2, hi, and h2 are taken. Permeability is computed from... 

Several investigations present relative rankings of permeability coefficients observed for several different animal species (for example, Marzulli etal., 1969 Wester and Noonan, 1980). Although these rankings agree that skin from most of the animal species studied are more permeable than human skin, the relative order of the various species and the quantitative results are often inconsistent. Many rankings are derived from permeability coefficients measured in vivo, from different... 

The permeability of a device can be determined from flow rate, viscosity, column length and pressure as outlined in Section 2.2.5. Now we have accomplished what we have set out to do we have linked the performance parameter, the speed of analysis and the pressure to each other. All performance parameters can thus be determined from externally measurable observations without reference to the internal content of the chromatographic device ... 

The theoretical considerations summarized above indicate that the diffusion structural analysis can be applied to the investigation of processes taking place in solids or on their surfaces. Any process in a solid or its phase boundary leading to a change in either the surface and/or changes in the inert gas diffusivity (permeability) becomes observable from the DSA measurements. 

A second, and we believe more probable, explanation is that the hydrated polymer molecules are too large to pass some of the tight, connate water-saturated pores. These colloidal particles could physically block the smaller capillaries, thus making displacement of the connate water very difficult at best. The reduced relative permeability at residual oil to polymer water as compared to normal water gives some support to this argument. This explanation is essentially in agreement with the arguments of various authors )in support of their observed polymer solution mobilities which were lower than expected from viscosity measurements. 

It should be noted also that the intercept is difficult to determine accurately because of large potential experimental error in observing the time of the start of filtration and the time-volume correspondence during the first moments when the filtration rate is high. The value of / calculated from the intercept may vaiy appreciably from test to test, and will almost always be different from the value measured with clean medium in a permeability test. 

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