The Effective Permeability Coefficient

The first-order absorption rate constant introduced above may be directly related to the effective permeability coefficient (Peff) using 

This can be further simplified if it is assumed that there is no accumulation of drug on the blood side (i.e. CJ ) or the portal blood is considered 

More generally, this relationship is used to define the overall rate of absorption along the entire GIT as per 

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In PAMPA, the effective permeability coefficient, Pe, is related to the membrane and ABL permeability coefficients, P and Pabl. respectively, as... 

The effective permeability coefficient is composed of the permeability coefficients for the various transport barriers in series—the ABLs, the cell monolayer, and the filter support ... 

The permeability coefficients, PD and PR, are influenced by hydrodynamics. Depending upon the geometric symmetry or asymmetry of stirring in the donor and receiver chambers, their values may be equal or unequal. To analyze these situations, let us define PAm, as the effective permeability coefficient of the ABLs therefore, the geometric average of the mass transfer resistance of the ABLs is... 

Figure 17 depicts the rapid flux of sucrose across the filter into the receiver. Upon treatment of the data with Eq. (7), the effective permeability coefficient (Pe) is found to be 2.29 X 10 4 cm/sec, which takes into account the filter and the ABLs on both sides of the filter hence,... 

As described in Section II, the effective permeability coefficient is expressed as... 

The summary of Pe values for the steroids as a function of stirring rates is found in Table 11 and their correlations with log PC (n-octanol-water) in Figure 20. The transport kinetics of the relatively hydrophilic hydrocortisone and dexa-methasone are controlled by passive diffusion across the cell monolayer. On the other hand, the Pe values of testosterone and progesterone are highly dependent on stirring rate. The results for testosterone are used to obtain the relationships between the effective permeability coefficients of the ABL on the donor and receiver sides and the stirring rate, using the linear expression (see Eq. (69)]... 

Figure 21 Linearized double reciprocal plot of the effective permeability coefficients and corresponding stirring rates to determine the power dependency of the stirring rate and mass transfer resistances for the aqueous boundary layers and the Caco-2 cell monolayer in the Transwell system. 

Figure 24 shows a schematic diagram of the pathways the various species of a permeant (e.g., weak base) take during their passage across the cell monolayer-filter support system. From a general point of view, the effective permeability coefficient may be expressed in the form... 

Figure 26 Correlation of the effective permeability coefficients of (3-blockers determined at pH 6.5 (O) and 7.4 ( ) with stirring rates and log partition coefficients (n-octanol/buffer at pH 6.5 and 7.4). APL, alprenolol ATL, atenolol PDL, pindolol PPL, propranolol.

The effective permeability coefficient of the diester, as viewed from the donor side, can be found by treating the data with Eq. (113) hence,... 

Figure 34 Effective cell partition coefficient of PNU-78,517 as a function of bovine serum albumin concentration. The inset shows the relationship between the effective permeability coefficient (Pe) of appearance and BSA concentration or the fraction of free drug. These data were obtained from the uptake data shown in Figure 33. [Redrawn from Raub et al. (1993) with permission from the publisher.]...

The initial conditions are CD = CD(0) at t = 0 and CR = 0 at t = 0. Efforts to obtain analytical solutions are tedious and unnecessary. By applying the change in concentrations (or mass) in the donor and receiver solutions with time to the Laplace transforms of Eqs. (140) and (141), the inverse of the simultaneous transformed equations can be numerically calculated with appropriate software for best estimates of a, (3, and y. It is implicit here that P Pap, Pbh and Ke are functions of protein binding. Upon application of the transmonolayer flux model to the PNU-78,517 data in Figure 32, the effective permeability coefficients from the disappearance and appearance kinetics points of view are in good quantitative agreement with the permeability coefficients determined from independent studies involving uptake kinetics by MDCK cell monolayers cultured on a flat dish... 

The purpose of this report is to present results on (a) the effect of ethanol on the transport of 8-estradiol across hairless mouse skin and (b) the effect upon the effective permeability coefficient as solvent compositions are independently varied in the donor and receiver chambers. Also, since there is evidence for pore formation, at least at the highest ethanol levels, a novel pore model... 

Experimental Results and Comparisons with the Classical Lipid Barrier Model. Some typical experimental data are presented in Figure 1 for the transport of g-estradiol. In each of the experiments a lag-time of 1.5 to 2.5 hours were followed by linear steady state fluxes. The effective permeability coefficient, Peff> was calculated from such data using Equation 1 under sink conditions (i.e., Cj/K Cr/Kr where, Kj is the partition coefficient between membrane and donor phase and Kr the partition coefficient between membrane and receiver phase.)... 

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