Curiously, the increase in the relative amount released was caused by a pair of substances from exactly opposite BCS classes: ASC with high solubility and high permeability and NX with low solubility and low permeability. The same was true for the two substances that reduced the relative amount released: HCTZ with a low solubility and high permeability and KM with a high solubility and low permeability. These results suggest that solubility/permeability of the co-permeating substance alone is insufficient to determine its effect on the quantity released of the fluorescent probe. Clearly, both antagonistic and synergistic effects between the permeants exist, and these are sufficiently strong to change CF membrane partitioning 2-5x in both directions, and permeability up to 2x upwards and up to 6x downwards (Table ). From the point of view of pharmacokinetics, such changes due to drug-membrane interaction could have dramatic therapeutic implications and could potentially lead to incorrect prescription and dosing Ascorbic acid (ASC) was added only by the aqueous route and caused CF permeability to be approximately doubled while the partition coefficient remained the same within the measurement error. Ascorbic acid is predominantly present in the anionic form (Table ).