Lipophilicity behaviour of the Zwitterionic antihistamine cetirizine in phosphatidylcholine liposomes/water systems.
OBJECTIVE
The partitioning of cetirizine in a phosphatidylcholine liposomes/water system was compared with that of hydroxyzine and acrivastine to gain insight into the mechanisms of interaction of its various electrical species with membranes.


METHODS
The lipophilicity profiles of the compounds were obtained from equilibrium dialysis and potentiometry, and compared with changes in NMR relaxation rates.


RESULTS
The neutral form of hydroxyzine interacted mainly via hydrophobic interactions with the bilayer lipid core of the membrane, whereas for the cationic form both hydrophobic and electrostatic interactions were involved. Zwitterionic and anionic cetirizine were less lipophilic than its cation, which behaved like the corresponding species of hydroxyzine. Zwitterionic cetirizine interacted more by weak electrostatic interactions with the polar headgroups of phospholipids than by hydrophobic interactions with the membrane interior. The lipophilicity of its anion reflected the balance of repulsive electrostatic interactions between the carboxylate and phosphate groups and the hydrophobic interactions with the lipid core.


CONCLUSIONS
The study confirms that various mechanisms influence the interaction of solutes with liposomes. Combining experimental techniques and using suitable reference compounds proves useful.
Plember van Balen
G
G
Institut de Chimie Thérapeutique, Section de Pharmacie, Université de Lausanne, Switzerland.
Caron
G
G
Ermondi
G
G
Pagliara
A
A
Grandi
T
T
Bouchard
G
G
Fruttero
R
R
Carrupt
P A
PA
Testa
B
B
D017332:Cetirizine / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003956:Dialysis; D004655:Emulsions; D005452:Fluoresceins / Q000737:chemistry; D006634:Histamine H1 Antagonists / Q000737:chemistry*; D006919:Hydroxyzine / Q000737:chemistry; D007202:Indicators and Reagents; D008081:Liposomes / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D010713:Phosphatidylcholines; D011199:Potentiometry; D014311:Triprolidine / Q000031:analogs & derivatives* / Q000737:chemistry; D014867:Water
D004655:Emulsions; D005452:Fluoresceins; D006634:Histamine H1 Antagonists; D007202:Indicators and Reagents; D008081:Liposomes; D010713:Phosphatidylcholines; D014867:Water; D014311:Triprolidine; D006919:Hydroxyzine; C043648:acrivastine; C007740:fluorexon; D017332:Cetirizine