log P0CT - log P0CT

Figure 5.8 Comparison of liposome diff to octanol diff functions of substituted phenols [382,383]. [Avdeef, A., Curr. Topics Med. Chem., 1, 277-351 (2001). Reproduced with permission from Bentham Science Publishers, Ltd.]

groups of the phospholipids, an effect they preferred not to call ''ion pairing.'' Undeniably, the nature of the charged-species partitioning into phospholipid bilayers is different from that found in octanol.

In a later study, Austin et al. [442] effectively were able to reconcile the ionic strength differences between their study and that of Alcorn et al. [433], using a Gouy-Chapman model. When the drug concentration in the membrane is plotted against the drug concentration in water, the resultant hyperbolic curve shows a lessening slope (log D) with increasing drug concentration (10~6 to 10~4 M) when there is no background salt. This is consistent with the interpretation that surface-bound charged drug repulsion attenuates additional charged drug partitioning. Bauerle and Seelig [395] and Thomas and Seelig [397] observed hyperbolic curves with drug concentrations exceeding 1 p.M. The addition of 0.15 M NaCl mitigates the effect substantially, allowing for higher drug concentrations to be used.

Avdeef et al. [149] and Balon et al. [385,386] reported log pLm and log P^Pm values of a number of drugs, determined by the pH-metric method, using both LUVs and SUVs, in a background of 0.15 M KCl.

Escher and colleagues [383,384] reported SIP values for a large series of substituted phenols, using DOPC SUVs and the equilibrium dialysis/centrifugation method. Figure 5.8 is a plot of diffmem versus diffoct for the series of phenols studied by Escher. It appears that knowing the octanol diff values can be useful in predicting the membrane values, and for phenols the relationship is described by diffm

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