Erythrocytes partitioning

S. Urien, E. Albengres, A. Comte, J. R. Kiechel, and J. P. Tillement, Plasma protein binding and erythrocyte partitioning of nicardipine in vitro. J. Cardiovasc. Pharmacol. 7 891-898 (1985). 

MuUersman, G. Derendorf, H. Rapid analj sis of ranitidine in biological fluids and determination of its erythrocyte partitioning. J.Chromatogr., 1986, 381, 385—391... 

Chatelain, R Laruel, R., Amiodarone partitioning with phospholipid bilayers and erythrocyte membranes, J. Pharm. Sci. 74, 783-784 (1985). 

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). 

Maximum binding capacity of erythrocytes Half-saturation concentration Partition coefficients for blood/tissue kinetics Blood/liver Blood/kidney... 

The importance of lipids in membrane structure was established early in the 20th century when pioneering biophysicists established positive correlations between cell membrane permeabilities to small non-electrolytes and the oil/water partition coefficients of these molecules. Contemporary measurements of the electrical impedance of cell suspensions suggested that cells are surrounded by a hydrocarbon barrier, which was first estimated to be about 3.3 nm thick. This was originally thought to be a lipid monolayer. Among the pioneering biophysical experiments were those that established that the ratio of the area of a monolayer formed from erythrocyte... 

Gryns (1896), Hedin (1897), and especially Overton (1900) looked at the permeability of a wide range of different compounds, particularly non-electrolytes, and showed that rates of penetration of solutes into erythrocytes increased with their lipid solubility. Overton correlated the rate of penetration of the solute with its partition coefficient between water and olive oil, which he took as a model for membrane composition. Some water-soluble molecules, particularly urea, entered erythrocytes faster than could be attributed to their lipid solubility—observations leading to the concept of pores, or discontinuities in the membrane which allowed water-soluble molecules to penetrate. The need to postulate the existence of pores offered the first hint of a mosaic structure for the membrane. Jacobs (1932) and Huber and Orskov (1933) put results from the early permeability studies onto a quantitative basis and concluded molecular size was a factor in the rate of solute translocation. 

Distribution - In vitro orlistat was greater than 99% bound to plasma proteins (lipoproteins and albumin were major binding proteins). Orlistat minimally partitioned into erythrocytes. 

Liao, K. and Yin, M., Individual and combined antioxidant effects of seven phenolic agents in human erythrocyte membrane ghosts and phosphatidylcholine liposome systems importance of the partition coefficient, J. Agric. Food Chem., 48, 2266, 2000. 

On the other hand toluene (4) and 5-methoxy-indole (5) would not be considered very similar from a conventional point of view, yet their hemolytic activity is the same (logl/C = 1.93, where C is the minimal molar concentration which causes 100% hemolysis in rabbit erythrocytes l)). Obviously, topological similarity or dissimilarily is not always a factor which is relevant for biological activity. In the present example the relevant feature is a physicochemical property of the compounds, i.e. lipophilicity as expressed by the octanol/water partition coefficient... 

There are many assumptions and parameter choices involved in the calculation of rg. For instance, we let Ames/A be 20, whereas many leaves have values from 30 to 40 the latter ratios would reduce rj c to 70 to 90 sm 1. The cell walls of some mesophyll cells are only 0.07 pm thick, which would decrease rg to less than 10sm-1. Permeability coefficients of the plasma membrane of mesophyll cells for CO2 have not been adequately measured. In this regard, Pj is equal to DjK/Ax (Eq. 1.9), where the diffusion coefficients of H20 and CO2 in the plasma membrane are probably about the same (within a factor of 2 of each other), the partition coefficient for CO2 is most likely at least 10 times higher than A 0, and Axpm is the same for H20 and C02- Because Pg] can be 10-4 m s-1 (see Chapter 1, Section 1.4B), our assumed value of 5 x 10-4 m s-1 for Pg may be to° low—we noted in Chapter 1 (Section 1.4B) that Pj for another small molecule, O2, crossing erythrocyte membranes can have an extremely high value of 0.3 ms"1. A higher value for Pg will decrease our estimate for rg and thus for rgcy... 

For drugs like NAPA that partition preferentially into red blood cells and are fully accessible to the dialyzer from both plasma and erythrocyteS/ the effective plasma flow will not be less than but will exceed measured blood flow (12). 

Referring once more to the effect of the aqueous medium composition upon the relative hydrophobicity of biological solutes, the correlation relationship establish-ecj io3,u6) between the effects of the medium ionic composition on the relative hydrophobicity of serum albumins of various origin and on that of erythrocytes from the same species should be noted. The ionic strength value of the medium in the aqueous ficoll-dextran biphasic system has been used as a quantitative index of the ionic composition of the system, and the ionic composition was varied from 0.11 M phosphate buffer to 0.15 M NaCl in 0.01 M buffer at pH 7.4 116). Partition coefficients of cells in an aqueous polymeric biphasic system are determined as the ratio of a number of the cells in the phase to that of the cells present at the interphase 90). Specific features of the partition behavior of cells in aqueous biphasic systems are discussed in detail elsewhere (see, e.g., Ref. 90 91). It has been established 116) that erythrocytes of different species are distributed in the aqueous ficoll-dextran biphasic system according to the following equation ... 

---