Regional permeability coefficients

Figure 17.4 is a representation of regional permeability coefficients of 19 drugs with different physicochemical properties determined by Ungell et al. by using excised segments from three regions of rat intestine jejunum, ileum, and colon [62],... 

The solubility-diffusion theory assumes that solute partitioning from water into and diffusion through the membrane lipid region resembles that which would occur within a homogeneous bulk solvent. Thus, the permeability coefficient, P, can be expressed as... 

Only a subset of the parameter values in the O Flaherfy model require inputs from the user to simulate blood and tissue lead concentrations. Lead-related parameters for which values can be entered into the model include fractional absorption from the gastrointestinal tract partition coefficients for lead in nonbone tissues and in the surface region of bone maximum capacity and half-saturation concentration for capacity-limited binding in the erythrocyte elimination clearance fractional clearance of lead from plasma into forming bone and the restricted permeability coefficients for lead diffusion within bone, from plasma into bone, and from bone into plasma (O Flaherty 1991a). 

Differential scanning calorimetric and infrared spectroscopic investigations of intact stratum corneum, extracted lipids and keratinized protein residue sheets suggested the thermal transitions occurring within the 30 to 70°C region were associated with increased molecular mobility of the lipids. The permeability coefficients of lipophilic molecules through hairless mouse skin increased by several orders of magnitude over the same temperature... 

Starting with a known cj outside a cell and determining the internal concentration both initially (i.e., for t = 0) and at some subsequent time , we can calculate P from Equation 1.12 if AIV is known. Even when AN is not known, the relative permeability coefficients for two substances can be determined from the time dependencies of the respective cj s. The previous derivation can be extended to the case in which cj is zero. In that case, PjAtIV equals ln[cj(0)/cj( )], an expression that can be used to describe the diffusion of a photosynthetic product out of a chloroplast or some substance from a cell into a large external solution initially devoid of that solute. Such studies can be facilitated by using radioactive tracers, which usually are initially present only in one region. 

The rate of transmembrane diffusion of ions and molecules across a membrane is usually described in terms of a permeability constant (P), defined so that the unitary flux of molecules per unit time [J) across the membrane is 7 = P(co - f,), where co and Ci are the concentrations of the permeant species on opposite sides of membrane correspondingly, P has units of cm s. Two theoretical models have been proposed to account for solute permeation of bilayer membranes. The most generally accepted description for polar nonelectrolytes is the solubility-diffusion model [24]. This model treats the membrane as a thin slab of hydrophobic matter embedded in an aqueous environment. To cross the membrane, the permeating particle dissolves in the hydrophobic region of the membrane, diffuses to the opposite interface, and leaves the membrane by redissolving in the second aqueous phase. If the membrane thickness and the diffusion and partition coefficients of the permeating species are known, the permeability coefficient can be calculated. In some cases, the permeabilities of small molecules (water, urea) and ions (proton, potassium ion) calculated from the solubility-diffusion model are much smaller than experimentally observed values. This has led to an alternative model wherein permeation occurs through transient hydrophilic defects, or pores , formed by thermal fluctuations of surfactant monomers in the membrane [25]. 

Figure 14.9 Sample cumulative skin permeation patterns following finite and infinite dosing regimes. With infinite dose, permeation normally reaches a steady-state flux region, from which it is possible to calculate permeability coefficients and diffusional lag times. In finite dosing the permeation profile normally exhibits a plateauing effect as a result of donor depletion.

Membrane performance is a trade-offbetween membrane selectivity and membrane productivity. Membrane selectivity, a (=A/B), is defined by the ratio of permeability of components through the membrane where A is the water permeability coefficient and B is the solute permeability coefficient. In the case of RO and NF membranes, water/NaCl selectivity for seawater RO membranes is about 10,000. The higher the selectivity, the lower the permeate flux or productivity. This relationship for various RO membranes used with dilute NaCl solution is shown in Figure 1.6. The shaded regions refer to different feed concentrations and to different types of membranes. The data is fairly independent of the feed concentration but is a function of the physical and chemical properties of the membrane. 

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