Apparent permeability constant

The permeability constant has been defined for steady state conditions, and at times before this is reached a smaller apparent permeability constant will be measured. Hence, when measuring permeability constant or transmission rate it is necessary to wait until the steady state has been... 

The evaluation of the apparent ionization constants (i) can indicate in partition experiments the extent to which a charged form of the drug partitions into the octanol or liposome bilayer domains, (ii) can indicate in solubility measurements, the presence of aggregates in saturated solutions and whether the aggregates are ionized or neutral and the extent to which salts of dmgs form, and (iii) can indicate in permeability measurements, whether the aqueous boundary layer adjacent to the membrane barrier, Umits the transport of drugs across artificial phospholipid membranes [parallel artificial membrane permeation assay (PAMPA)] or across monolayers of cultured cells [Caco-2, Madin-Darby canine kidney (MDCK), etc.]. 

Formulation Apparent permeability rate constant, kp SE, h 1 First-order dissolution rate constant, kd SE, h-1 = SE... 

Figure 10.2 Apparent permeability coefficients (Papp) observed in vitro across Calu-3 ( ) [62] and 16HBE14o- (o) [72] cell layers vs. in vivo rate constants (Ka) determined for absorption from the rat lung after intratracheal delivery of various molecules.

Widdas s quantitative model of the simple carrier was able to explain a number of earlier observations and to make predictions about what would be observed in more complex experiments on membrane transport. Thus it was a highly productive scientific insight. One of the earlier, apparently anomalous, results that the theory explained was the dramatic fall of membrane permeability found for solutes which were rapidly transported as solute concentration was increased. For example, in the human red blood cell, Wilbrandt and colleagues had previously measured a permeability constant for glucose which was 1000 times higher in dilute solutions of glucose than it was in a concentrated solution. This phenomenon, subsequently called saturation kinetics, is formally equivalent to the fall, as substrate concentration increases, in the proportion of substrate converted to product by a limited amount of an enzyme. 

Here, P s and /<. s are the cesium permeability in the ith transport experiment and in the first run, respectively, and R = (Vfeed+ Vslnp)/VSLM, Vfeed, Vstrip, and VSLM are the volumes of feed and stripping aqueous phases and the volume of organic phase in the membrane, respectively. Kp is the apparent partition constant of the carrier between the SLM and both aqueous and stripping solutions. Values of this apparent partition constant can be deduced via linear regression of log PCs versus (i-1). They are equal to 128,100, 29,100, 106,700, and 295,000, respectively, for decyl-benzo-21-crown-7, calix[4]arene-bis(crown-6), calix[4]arene-bis(benzo-crown-6), and calix[4]arene-bis(naphtho-crown-6). Calix[4]arene-bis(crown-6) rapidly leaked off the membrane... 

Apparent maximal Apparent permeability Michaelis constant in Maximal transport rate... 

The apparent permeability coefficient Papp is related to the first-order rate constant for the disappearance of drug from vaginal lumen (ky) as follows ... 

Apparent permeability Ionization constant in water Solubility... 

The common element of most such studies is the dissection and isolation of scleral tissue, followed by placement of the sclera between two chambers representing the episcleral surface and the uveal surface. One chamber contains the labeled compound, and the other chamber is sampled periodically after steady-state flux is attained. Some studies have used an apparatus where the chambers are constantly stirred. This may yield a higher apparent permeability by utilizing an unmixed depot on the tissue surface where static boundary layers may exist. However the impact of boundary layers on high molecular weight tracers is not expected to be significant, especially when temperature fluctuations are minimal (26,27). 

Diffusion processes are related to chemical kinetics on the one hand, and to sorption and solution equilibria on the other. There are available excellent surveys dealing with chemical kinetics and also with sorption equilibria. No previous text has attempted to correlate and summarise diffusion data in condensed phases, save briefly and in relation to one or other of these fields. It is apparent that the study of diffusion touches upon numerous aspects of physico-chemical research. There are in general two states of flow by diffusion— the so-called stationary and non-stationary states. From the former one derives the permeability constant (quantity transferred/unit time/unit area of unit thickness under a standard concentration or pressure difference) and from the latter the dijfusion constant. The permeabihty constant, P, and the diffusion constant, D, are related by... 

Bacillus thuringiensis produces a variety of organic compounds which are toxic to the larvae of certain susceptible insect hosts. Among the toxic entities are proteinaceous crystals, probably three soluble toxins, and certain enzymes. The protein material is the major toxin active in killing lepidopterous larvae. The protein is formed by the cells apparently in close synchrony with sporulation, and its nature is a constant function of bacterial strain. The mode of action of the protein is under study. The sequence of events in the pathology observed is probably solubilization of the crystal (enzymatic or physical)—>liberation of toxic unit—>alteration of permeability of larval gut wall— change in hemolymph pH—>invasion of hemolymph by spores or vegetative cells of the bacterium. 

The permeability coefficient Kpcr is just the flux divided by Cw. It is apparent that the permeability coefficient is linear with P for small distribution coefficients and constant for large P. Thus, for small P the epithelium is the barrier, and for large P the stroma is the barrier. A fit for steroid permeability is shown in Fig. 12, where the regression analysis gave De = 1.4 x 10 9cm2/s and Ds = 2.0 x 10 6cm2/s for 4 = 4 x 10 3 cm and 4 = 3.6 x 10 2 cm [205]. These values for the diffusion coefficients are reasonable compared with those of aqueous gels and lipid membranes. 

P = permeability P0 = intrinsic permeability Ep = apparent activation energy R - the gas constant T = absolute temperature... 

Dithiocarbamates and xanthates form particularly stable, neutral complexes with Cu(II), Cd(II) (and also Ni, Hg, Pb), which are membrane permeable and increase the apparent bioaccumulation of these metals [13]. In the series of sulfoxine, oxine, and chloroxine, the hydrophobicity of the neutral and the charged form, as well as of the Cu complex, increases. While the sulfoxine is not hydrophobic and does not modulate copper toxicity [220], the Cu-oxine complex is hydrophobic with an octanol-water partition constant, log Kok, of 1.7 [221] or 2.6 [222]. Chloroxine can be assumed to be even more hydrophobic, but so far its influence on uptake and toxicity has not been investigated. Uptake of Cu2+ into unilamellar liposomes was increased in the presence of 8-hydroxy-chinoline, and decreased again after adding HA [223],... 

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