title: Lipophilicity behaviour of the Zwitterionic antihistamine cetirizine in phosphatidylcholine liposomes/water systems.
abstract: 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.
authors.affiliation: Institut de Chimie Thérapeutique, Section de Pharmacie, Université de Lausanne, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Plember van Balen
authors.forename: G
authors.initials: G
authors.lastname: Caron
authors.forename: G
authors.initials: G
authors.lastname: Ermondi
authors.forename: A
authors.initials: A
authors.lastname: Pagliara
authors.forename: T
authors.initials: T
authors.lastname: Grandi
authors.forename: G
authors.initials: G
authors.lastname: Bouchard
authors.forename: R
authors.initials: R
authors.lastname: Fruttero
authors.forename: P A
authors.initials: PA
authors.lastname: Carrupt
authors.forename: B
authors.initials: B
authors.lastname: Testa
mesh_terms: 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
chemical_list: 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