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Partition and distribution coefficients of solutes and drugs in brush border membrane vesicles.
- Source :
-
Biochemical pharmacology [Biochem Pharmacol] 1993 May 05; Vol. 45 (9), pp. 1775-82. - Publication Year :
- 1993
-
Abstract
- Partition and distribution coefficients (log P, log D) into rat small intestinal brush border membrane (BBM) were measured for a variety of ionizable and non-ionizable drugs and solutes using a novel technique. The log P values were compared with those determined with model solvents, octanol and propylene glycol dipelargonate (PGDP). Non-ionizable solutes with log P values up to 3.0 showed that octanol was a better model for partition into the BBM than PGDP. With one exception, BBM partition coefficients of greater than 3 were not observed, even for solutes with log P values in model solvents that were greater than 5. Liposomes prepared from BBM lipids, or synthetic lipid mixtures of similar composition to BBM, demonstrated similar trends in partition coefficients to the intact BBM. Two cationic drugs, Atenolol and Xamoterol were investigated for partition into BBM lipid liposomes. An apparent enhancement of log D with respect to octanol was attributed to a "surfactant-like" orientation in the membrane and an interaction of the ionized drug with anionic phospholipid head groups. The anionic drug Proxicromil shows the expected decrease in log D with increasing pH, at low NaCl concentrations. Changes in electrophoretic mobility of liposomes after incorporation of Proxicromil into them were consistent with the negative charge of the ionized drug being at the membrane surface. It was concluded that Proxicromil also associates with membranes in a "surfactant-like" orientation and that increased extraction with increasing NaCl concentrations is a result of ionic strength effects. Partition of solutes into BBM vesicles is more complex than into organic solvents and probably represents an important step in overall intestinal permeation of solutes.
- Subjects :
- 1-Octanol
Acetonitriles
Animals
Cell Membrane Permeability
Chromones pharmacokinetics
Female
Hydrogen-Ion Concentration
Intestinal Absorption
Liposomes
Male
Mathematics
Methanol
Octanols
Osmolar Concentration
Rats
Rats, Sprague-Dawley
Solvents
Water
Intestinal Mucosa metabolism
Microvilli metabolism
Pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 0006-2952
- Volume :
- 45
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Biochemical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 8494536
- Full Text :
- https://doi.org/10.1016/0006-2952(93)90433-w