Air-lipid partition coefficient

Data from McLachlan, 1996. Also given are the estimated air-lipid partition coefficients and the used Aa jpH, values.)... 

The simplest way to predict the lipid/ water partition coefficient, Kiw, of a drug is based on measurements of the surface pressure, ttd, of the drug as a function of its concentration in the aqueous subphase (Gibbs adsorption isotherm). The Gibbs adsorption isotherm provides the air/water partition coefficient, Kaw, and the cross-sectional area, Ad of the drug and allows calculation of the lipid/water partition coefficient, K]w, according to Eq. (6) [59] ... 

The presence of a transporter can be assessed by comparing basolateral-to-apical with apical-to-basolateral transport of substrates in polarized cell monolayers. If P-gp is present, then basolateral-to-apical transport is enhanced and apical-to baso-lateral transport is reduced. Transport experiments are in general performed with radioactively labeled compounds. Several studies have been performed with Caco-2 cell lines (e.g. Ref. [85]). Since Caco-2 cells express a number of different transporters, the effects measured are most probably specific for the ensemble of transporters rather than for P-gp alone. P-gp-specific transport has been assayed across confluent cell layers formed by polarized kidney epithelial cells transfected with the MDR1 gene [86], Figure 20.11 shows experimental data obtained with these cell lines. A rank order for transport called substrate quality was determined for a number of compounds [86]. The substrate quality is a qualitative estimate, but nevertheless allows an investigation of the role of the air/water (or lipid/water) partition coefficient, log Kaw, for transport as seen in Fig. 20.11(A). For most of the compounds, a linear correlation is observed between substrate quality and log Kaw- However, four compounds are not transported at all despite their distinct lipophilicity. A plot of the substrate quality as a function of the potential of a... 

Chloroform is lipid soluble and readily passes through cell membranes, causing narcosis at high concentrations. Blood chloroform concentrations during anesthesia (presumed concentrations 8,000-10,000 ppm) were 7-16.2 mg/mL in 10 patients (Smith et al. 1973). An arterial chloroform concentration of 0.24 mg/mL during anesthesia corresponded to the following partition coefficients blood/gas, 8 blood/vessel rich compartment, 1.9 blood/muscle compartment, 1.9 blood/fat compartment, 31 blood/vessel poor compartment, 1 and blood/liver, 2 (Feingold and Holaday 1977). Recently, partition coefficients were calculated for humans based on results in mice and rats, and in human tissues in vitro blood/air, 7.4 liver/air, 17 kidney/air, 11 and fat/air, 280 (Corley et al. 1990). 

Freshwater mammals such as heaver may leave odors on the surface of their ponds and olfactorily sample the water or layer of air immediately above it. Lipids on water may form micelles, small blobs of molecules (from Latin mica, a grain, crumb, morsel) that enhance evaporation into the air layer by increased chemical potential. Some seahirds hunt hy odor (e.g. Hutchison and Wenzel, 1980 Nevitt, 1999). They may respond to prey volatiles (from krill, squid, or fish) that rise to the water surface and evaporate into the air. The air-water equilibrium for dilute solutions can be expressed by using partition coefficients, relative volatility, or Henry s law (Thibodeaux, 1979). 

Pulmonary absorption of volatile anesthetics across the alveolar-capillary barrier is very rapid because of the relatively high lipid-water partition coefficients and small molecular radii of such agents. The driving force for diffusion is a combination of the blood-air partition coefficient (which is a measure of the capacity of blood to dissolve drug) and the difference in partial pressure between the alveoli and the arterial and venous blood. Agents with high blood-air partition coefficients require more drug to be dissolved in the blood for equilibrium to be reached. 

In the laboratory, we usually determine Kl2 from the slope of C versus C2 over a range of concentrations. Partition coefficients can be measured for essentially any two-phase system air-water, octanol-water, lipid-water, particle-water, and so on. In situ partition coefficients also can be measured where site-specific environmental conditions might influence the equilibrium phase distribution. 

The octanol-air partition coefficient (KOA) has played an important role in the study of plant-air partitioning. At the end of the 1980s, when interest in this subject started to grow, octanol was already well established as a model for the partitioning properties of organic carbon and lipids in aquatic systems. Several researchers borrowed from this experience and postulated that the partitioning properties of the hydrophobic or lipid-like portions of plants also could be modelled using octanol (Schramm et al., 1987 Paterson and Mackay, 1989 McLachlan et al., 1989). Since the partner phase was air, the octanol-water partition coefficient could not be used and it became necessary to define an octanol-air partition coefficient. 

Riederer (1990) published a more complex method based on two lipid-like compartments, an acylglycerol lipid compartment and a cuticle compartment. The acylglycerol-air partition coefficient was assumed to equal Kow/Kaw, while measured values of the cuticle-water partition coefficient were employed for the cuticle compartment. Riederer (1995) later modified this model to include a predictive equation for the cuticle-water partition coefficient, based on Kerler and Schonherr s measurements (1988) of eight chemicals with log KqW values ranging from 1.92 to 7.86. They used isolated citrus and rubber plant leaf cuticles as well as tomato and green pepper fruit cuticles. The resulting equation is... 

Different approaches have been published regarding the prediction of partition coefficients on the basis of physicochemical parameters of compounds [26-29], These authors described algorithms for the estimation of blood-air and tissue-blood partition coefficients. The most important descriptor for blood-tissue partitioning appears to be lipophilicity and can be described as a function of blood and tissue composition with regard to the lipid and water fractions. Charged molecules do not easily pass membranes passively however, weak bases appear to interact with the charges present at the hydrophilic moieties of phospholipids and can be transferred over the membranes in this way [28]. 

In Equation 10.11, C (t) is the concentration of the compound in the SC lipid phase at time t, 5 is its solubility in these lipids (taken to be the product of water solubility and octanol-water partition coefficient K a)> id b is a positive exponent with a value of about 2.7 (Kasting and Saiyasombati, 2001). The value of b was estimated based on an analysis of the Flynn skin permeability database (Johnson et al., 1997), which represents steady-state permeabilities obtained with hydrated human skin in vitro. It is possible that a somewhat higher value of b may apply for volatile disposition on air-dried skin if it is more size selective than hydrated skin. Such a refinement has not been attempted here. 

The uptake of organic contaminants by plants from biosolids-amended soil depends on the physicochemical properties of organic compoimds and the physiology of plants [92-95]. Plant uptake of organic chemicals and their distribution within plants have been shown to be affected by (1) the organic chemicals physicochemical properties, including solubility, vapor pressure, octanol-water partition coefficient Kow)> and Henry s law constants (iC ), (2) environmental conditions such as temperature, air disturbance and soil organic matter content, and (3) plant characteristics, for example the shape of the leaves, type of root system, and lipid and cuticle characteristics and contents [94]. 

The very low vapour pressure of DDT is largely offset by its large activity coefficient. Solubility thus plays a key role in determining the partitioning of chemicals from water to air, lipids and other phases such as soil and sediments. 

These data enable assessments to be made of how chemicals in a series will differ in their environmental behaviour as they partition between air, water and organic phases. As is discussed by Gobas et al. (1987) elsewhere in this text, extreme caution must be used when calculating partitioning coefficients into organic media when log exceeds 5. It is suspected that octanol then ceases to be a satisfactory surrogate for lipids and probably also for organic matter sorption. 

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