Membrane/water partition coefficients

Avdeef, A., Box, K. J., Comer, J. E., Hibbert, C., Tam, K. Y. pH-metric logP 10. Determination of liposomal membrane-water partition coefficients of ionizable drugs. Pharm. Res. 1998,... 

Membrane uptake of nonionized solute is favored over that of ionized solute by the membrane/water partition coefficient (Kp). If Kp = 1 for a nonionized solute, membrane permeability should mirror the solute ionization curve (i.e., membrane permeability should be half the maximum value when mucosal pH equals solute pKa). When the Kp is high, membrane uptake of nonionized solute shifts the ionization equilibrium in the mucosal microclimate to replace nonionized solute removed by the membrane. As a result, solute membrane permeability (absorption rate) versus pH curves are shifted toward the right for weak acids and toward the left for weak bases (Fig. 7). 

Gobas, F.A.P.C., Lahittete, J.M., Garofalo, G., Shiu, W.Y., Mackay, D. (1988) A novel method for measuring membrane-water partition coefficients of hydrophobic organic chemicals Comparison with 1-octanol-water partitioning. J. Pharm. Sci. 77, 265-272. 

Understanding and estimating membrane/water partition coefficients Approaches to derive quantitative structure property relationships, Chem. Res. Toxicol. 11 847 (1998). 

Derivation of Membrane-Water Partition Coefficients of a Charged or Neutral Compound or Species. 223... 

Since the membrane water partition coefficient is a relevant parameter for the pharmacokinetic behaviour, i.e. drug uptake, many more studies on the speciation of drugs at membrane interphases can be found in the... 

Principal differences between bulk media water and membrane water partition coefficients are listed in Table 2. These differences are essentially based on the several orders of magnitude difference in surface-to-volume ratio. In the liposomal system, charges built up due to sorption of charged species can be electrically neutralised by counter-ions from the electrolyte (diffuse double... 

Often, the concentration of compound or species i in the membrane is given in molality (mol kg ), which yields the membrane water partition coefficient, w (in units of dm kg 1) ... 

The major route for bioaccumulation of hydrophobic organic compounds in aquatic animals is passive diffusion over cell membranes. In fish, the gill epithelia are the predominant port of entry, with less than 40% of uptake across the skin [181]. Since permeability of the membrane is a direct function of the membrane-water partition coefficient and the diffusion coefficient across the membrane interior [182], the bioconcentration factor (logBCF) can be directly correlated with log K0Vl. or log Km%v for compounds with intermediate hydro-phobicity [183,184],... 

K Dimensionless membrane-water partition coefficient of species or compound i ... 

Estimation is easier and less time-consuming because use is made of empirical relationships between the BCF and physicochemical properties of the compound, such as water solubility (S) [42-48], Km, (solid organic carbon/water partition coefficient) [48], Kmw (membrane water partition coefficient), iipw (liposome water partition coefficient) [49], critical micelle concentration (CMC) [45], steric factors, molecular weight [47,48], and others. The most common regression method is the estimation of BCF from the octanol-water partition coefficient (Kovl) [18,42,44-48,50,51],... 

By using a PES with a different thickness, one can conveniently change the AV ratio. This approach permits some control over the time required to reach equilibrium concentrations. Bartkow et al. (2004) has reported an excellent example of the impact of ratio or thickness on the time to equilibrium. These investigators showed that a 200 pm thick PE sheet took twice as long to reach equilibrium in air as a 100 pm thick PE sheet. In theory, changing membrane thickness will not affect polymer diffusivity and equilibrium membrane-water partition coefficients (I mwS) or solubility coefficients ( p). However, in practice different values of (membrane-air partition coefficient) and membrane... 

Because neither nor are strong functions of the physical-chemical properties of the analytes (see below), the issue of which phase controls the uptake rate is primarily governed by the membrane-water partition coefficient, which varies between compounds by many orders of magnitude (Reynolds et al., 1990 Lefkovitz et al., 1996 Booij et al., 2003a). With increasing log Ko , there always will be a critical log Kov, value where the uptake rates will be controlled by the WBL instead of by the membrane. Next to /fmw (which is a compound specific property) it is important to note that rate control is also dependent on the magnitude of kw, which is determined by the hydrodynamical conditions prevailing at the membrane-water... 

A Avdeef, KJ Box, JEA Comer, C Hibbert, KY Tam. pH-Metric log P 10. Determination of liposomal membrane-water partition coefficients of ioniz-able drugs. Pharm Res 15 209-215, 1998. 

Vaes, W. H. J., E. U. Ramos, C. Hamwijk, I. von Holsteijn, B. J. Balaauboer, W. Seinen, H. J. M. Verhaar, and J. L. M. Hermens, Solid phase microextraction as a tool to determine membrane/water partition coefficients and bioavailable concentrations in in vitro system , Chem. Res. Toxicol., 10, 1067-1072 (1997). 

In terms of the characterization of the thermodynamic behavior, the phase diagram and the variation of response functions - for example specific heat and the membrane-water partition coefficients seen in crossing the phase diagram - are important indicators of the molecular interactions [49],... 

Vaes, W.H.J., Ramos, E.U., Verhaar, H.J.M., Cramer, C.J., and Hermens, J.L.M., Understanding and estimating membrane/water partition coefficients approaches to derive quantitative structure property relationships, Chem. Res. Toxicol., 11, 847-854, 1998. 

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