DOPC under Sink Conditions

Furthermore, the membrane retentions of the lipophilic probe molecules are dramatically decreased in the presence of the sink condition in the acceptor wells, as shown in Fig. 7.27. All molecules show R 35%, with progesterone and phenazo-pyridine showing the highest values, 34% and 26%, respectively. 

The combination of increased Pe and decreased %R allowed the permeation time to be lowered to 4 h, in comparison to the originally specified time of 15 h [547,550], a considerable improvement for high-throughput applications. The quality of the measurements of the low-permeability molecules did not substantially improve with sink conditions or the reduced assay times. 

2 DOPC with Dodecyicarboxyiic Acid under Sink Conditions 

The increase of negative charge from 0.6% to 1.1% wt/vol in dodecane (modeling the expected increase between BBM and BBB lipid compositions see Table 7.1) shows further increases to the permeabilities of the dramatically affected molecules, especially amiloride, which becomes effectively more permeable than piroxicam. 

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Tables 7.6-7.8 list the Pe, SD, and %R of the 32 probe molecules in the thirteen new PAMPA lipid models, one of which is 2% DOPC assayed under sink conditions (model 1.1). The latter model served as a benchmark for assessing the effects of negative membrane charge.

DOPC with Phosphatidic Acid under Sink Conditions... 

Introducing negative-charge phospholipids to the 2% DOPC at pH 7.4 improved the correlations significantly (models 5.0, 6.0, 7.0, 8.0, 9.0, 10.0). Sink conditions only marginally improved the correlations for the dodecylcarboxylic acid (1.1% DA) and phosphatidic acid (0.6% PA) models (models 6.1 and 7.1). The phospha-tidylglycerol (PG) models (models 9.1 and 10.1) did not correlate well under sink conditions. The modified Chugai model at pH 7.4 performed well (r2 0.60), but was unstable under sink conditions. 

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