Partitioning theory

It was assumed for a long time that molecules can only cross a membrane in their neutral form. This dogma, based on the pH-partition theory, has been challenged [42, 43]. Using cyclic voltammetry it was demonstrated that compounds in their ionized form pass into organic phases and might well cross membranes in this ionized form [44]. 

The pH-partition theory or nonionic permeability hypothesis was first described by Jacobs in 1940 [66]. According to this concept, only neutral, preferably nonpolar compounds are able to cross biological membranes. The transcellular permeability pH-profile is then essentially characterized by the membrane partition coefficient and the pKa of the compound. The simplest quantitative description of membrane permeation is given by ... 

An important extension of lipid-solute interaction components [20] to membrane partitioning is provided by solute molecular structure. Spacing between polar and nonpolar regions (Fig. 8) within a solute molecule may result in significant distortion of the KpDm product across the membrane polar headgroup/lipid core interface [21], Such interactions may be responsible for deviations from projected transport predictions based on simple partitioning theory translating to deviations from predicted absorption kinetics [1],... 

One of the original concepts governing oral absorption of organic molecules is the pH partition hypothesis . This hypothesis states that only the nonionized form of the drug is able to permeate the membranes of epithelial cells lining the GI tract [26], According to the classical pH-partition theory, permeability is expected to correlate not with the intrinsic partition coefficient but with the so-called distribution coefficient D of the solute [27], where D is defined as ... 

Ma, W.-C., A. Van Kleunen, J. Immerzeel, and P.G.-J. De Maagd. 1998. Bioaccumulation of polycyclic aromatic hydrocarbons by earthworms assessment of equilibrium partitioning theory in situ studies and water experiments. Environ. Toxicol. Chem. 17 1730-1737. 

Kramer, S. (2001). Liposome/water partitioning theory, techniques, and applications. In Pharmacokinetic Optimization in Drug Research Biological, Physicochemical, and Computational Strategies, eds. Testa, B., van Waterbeemd, H., Folkers, G. and Guy, R., Series, Yerlag Helvetica Chimica Acta, Zurich. 

Generally, to produce a biological response, a drug molecule must first cross at least one biological membrane. The biological membrane acts as a lipid barrier to most drugs and permits the absorption of lipid-soluble substances by passive diffusion while lipid-insoluble substances can diffuse if at all across the barrier only with considerable difficulty. The interrelationship of the dissociation constant, lipid solubility, and pH at the absorption site and absorption characteristics of various drugs are the basis of the pH-partition theory. 

Terrestrial BMOs have also been widely used for monitoring environmental contaminants. In particular, the lipid-like waxy cuticle layer of various types of plant leaves has been used to monitor residues of HOCs in the atmosphere. However, some of the problems associated with aquatic BMOs apply to terrestrial BMOs as well. For example, Bohme et al. (1999) found that the concentrations of HOCs with log KoaS < 9 (i.e., those compounds that should have attained equilibrium) varied by as much as 37-fold in plant species, after normalization of residue concentrations to levels in ryegrass (Lolium spp.). These authors suggested that differences in cuticular wax composition (quality) were responsible for this deviation from equilibrium partition theory. Other characteristics of plant leaves may affect the amount of kinetically-limited and particle-bound HOCs sampled by plant leaves but to a lesser extent (i.e., <4-fold), these include age, surface area, topography of the surface, and leaf orientation. 

The major pathway of drug transport across buccal mucosa seems to follow simple Fickian diffusion [17]. Passive diffusion occurs in accordance with the pH-partition theory. Considerable evidence also exists in the literature regarding the presence of carrier-mediated transport in the buccal mucosa [18,19]. Examination of Eq. (1) for drug flux,... 

The procedure is to calculate the B P or 1 4 isotope transfer in a stepwise manner using partition theory ... 

Passive Transcellular Pathway pH Partition Theory as the Basis of Understanding Membrane Permeability... 

Values recommended by Mackay et al. (1992) and Mackay and Callcott (1998) for the vapor pressures of a number of PAHs of atmospheric interest and several properties used in theoretical calculations of their gas-particle partitioning in ambient air are given in Table 10.6 for examples of their use, see discussion of gas-particle partitioning theory in Chapter 9.D and references cited above. 

These conditions are embodied in the pH-partition theory only nonionized lipid-soluble compounds will be absorbed by passive diffusion down a concentration gradient. Let us examine the three conditions in turn. 

Passive diffusion (lipid-soluble, noncharged molecules concentration gradient first order pH partition theory)... 

In the early 1980s, Yalkowsky and Valvani developed a partition theory (Yalkowsky and Valvani,... 

The next step in developing the solubility equation by partition theory is the estimation of the activity coefLcient of solute in watersolution. If an aqueous solution is equilibrated with octanol, then it can be shown th i can be related to the octanol-water partition coefLcient by... 

Goodman, M., and B.W. Barry. 1989. Lipid-protein-partitioning theory (LPP) theory of skin enhancer activity Finite dose technique. Int J Pharm 57 29. 

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