"All Pe and SD(Pe) are

in units of 10"

6 cm/s;

(nd) = compound


detected in the acceptor



show the most dramatic increases in going from 2% DOPC to 10% soy lipid membranes, somewhat higher in soy than in egg. Piroxicam shows less sensitivity to lipid changes. For higher phospholipid concentrations, all the acid permeabilities decrease.

The nonionizable molecules respond to the changes in the phospholipid content. Griseofulvin has the highest permeability in the lowest phospholipid-containing membranes. The most remarkable change of properties in going from 2% to 10%

phospholipid occurs with the membrane retention of the bases. Most of the bases are retained above 90% in all of the soy lecithin cases (<68% in dodecane). This is thought to be largely due to the added electrostatic attractions between positively charged sample molecules and the negatively-charged membrane constituents.

Acids show small, steady increases in membrane retention with increasing phos-pholipid content. Even though the acids are negatively charged at pH 7.4, as are a portion of the membrane constituents, the increasing phospholipid content draws the sample molecules in, due to increased hydrogen-bonding and any other lipophi-lic forces arising from the phospholipids (increased membrane-water partition coefficient). Decreased surface pH due to the membrane negative surface charge [457] may also play a role in increasing permeability of weak acids.

Neutral molecules show a range of retention properties between those of acids and bases. Progesterone membrane retention is very high in all cases. Griseofulvin and carbamazepine retention steeply increase with phospholipid content. The patterns of retention follow the lipophilicity properties of the molecules, as indicated by octanol-water apparent partition coefficients (Table 7.4).

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