0.3 cm2 cross-sectional area), and were able to demonstrate interesting predictions. Their PAMPA method appeared to be a satisfactory substitute for obtaining alkane-water partition coefficients, which are usually very difficult to measure directly, due to the poor solubility of drug molecules in alkanes. They applied the pH-based methods of Walter and Gutknecht [537] to extract the intrinsic permeability coefficients, P0, of the molecules they studied. A plot of log P0 vs. hexadecane-water log Kd is a straight line with a slope of 0.86 (r2 0.96), as shown in Fig. 7.11. Apparently, membrane retention was not measured in the original version of the method. A later measurement in our laboratory, where retention was considered, indicated a slope of 1.00, albeit with a slightly poorer fit (r2 0.92), as shown by the open circles in Fig. 7.11.

7.3.3 Brush-Border Lipid Membrane (BBLM) PAMPA Model (Chugai Model)

Sugano et al. [561,562] explored the lipid model containing several different phos-pholipids, closely resembling the mixture found in reconstituted brush border lipids [433,566] and demonstrated dramatically improved property predictions. The best-performing lipid composition consisted of a 3% wt/vol lipid solution in 1,7-octadiene (lipid consisting of 33% wt/wt cholesterol, 27% PC, 27% PE, 7% PS, 7% PI). The donor and acceptor compartments were adjusted in the pH interval between 5.0 and 7.4 [562]. With such a mixture, membrane retention is expected to be extensive when lipophilic drugs are assayed. The use of 1,7-octadiene in the assay was noted to require special safety precautions.

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