Permeability-limited transport

Figure 10.9 Permeability-limited transport across a low permeability capillary wall causes a slow approach to equilibrium between the plasma drug concentration (Cp) and tissue drug concentration (Cr).

The above iso-pH measurements are based on the 2% DOPC/dodecane system (model 1.0 over pH 3-10 range). Another membrane model was also explored by us. Table 7.16 lists iso-pH effective permeability measurements using the soy lecithin (20% wt/vol in dodecane) membrane PAMPA (models 17.1, 24.1, and 25.1) The negative membrane charge, the multicomponent phospholipid mixture, and the acceptor sink condition (Table 7.1) result in different intrinsic permeabilities for the probe molecules. Figure 7.40 shows the relationship between the 2% DOPC and the 20% soy iso-pH PAMPA systems for ketoprofen. Since the intrinsic permeability of ketoprofen in the soy lecithin membrane is about 20 times greater than in DOPC membrane, the flat diffusion-limited transport region of the log Pe... 

After five days, dopamine, L-tryptophan, and l-DOPA passively permeated through the membrane as indicated by fittings with a first-order kinetic process equation. After seven days of co-culture, occludin localizes at EC periphery, dopamine does not cross the barrier to any further extent, while the transfer of L-tryptophan and l-DOPA fits well with a saturable Michaelis-Menten kinetic process, thus indicating the involvement of a specific carrier-mediated transport mechanism. Permeation studies confirmed that culture of ECs in the presence of neurons induces the characteristic permeability limitations of a functional BBB. 

Transporters. If the NCEs are substrates for transporters, systemic or target tissue availability of the NCE may become limiting, and consequently influence the pharmacokinetics and pharmacodynamics of the NCE. Efflux transporters such as P-gp present in intestinal epithelia can have negative effects on the bioavailability of NCEs, particularly those that have poor membrane permeability. Whereas for NCEs that have good membrane permeability, efflux transporters do not play as critical role in intestinal absorption since a dose-dependent saturation of the efflux pump... 

When written in this form, Tt is positive for net transport into the tissue (e.g., distribution to tissue), or negative for net transport out of the tissue (e.g., absorption from site of administration). This equation for perfusion-limited transport clearly shows that for this limiting case, transport between the blood and tissue is dependent solely on the rate of blood perfusion (Q) and not on the permeability (P) or surface area for transport S) between the capillary lumen and tissue. 

Biocatalyst limitations Transport barriers - diffusion trough the cell membrane Permeability issues Highly complex cellular system Often product formation growth-associated Measurement and stability of enzyme activity Compartmentalization in some cases... 

Ideally, separators would present no resistance to ion transport. In practice, some resistance must be tolerated. Still, the resistance of the separator is usually insignificant relative to the transport limitations in the electrodes. Separator permeability is typically characterized by air permeability. The Gurley number expresses the time required for a specific amount of air to pass through a specific area of separator under a specific pressure (e.g., 10 mL through 1 in2 (6.45 cm2) at 2.3 cm Hg). This measurement depends on porosity, pore size, thickness, and tortuosity according to Eq. (1) [17] ... 

Permeability-pH profiles, log Pe - pH curves in arhficial membrane models (log Pjpp - pH in cehular models), generally have sigmoidal shape, similar to that of log Dod - pH cf. Fig. 3.1). However, one feature is unique to permeabihty profiles the upper horizontal part of the sigmoidal curves may be verhcally depressed, due to the drug transport resistance arising from the aqueous boundary layer (ABL) adjacent to the two sides of the membrane barrier. Hence, the true membrane contribution to transport may be obscured when water is the rate-limiting resistance to transport. This is especially true if sparingly soluble molecules are considered and if the solutions on either or both sides of the membrane barrier are poorly stirred (often a problem with 96-well microhter plate formats). 

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