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Ionic Partition Diagram of the Zwitterionic Antihistamine Cetirizine
Author(s) -
Bouchard Géraldine,
Pagliara Alessandra,
van Balen Georgette Plemper,
Carrupt PierreAlain,
Testa Bernard,
Gobry Véronique,
Girault Hubert H.,
Caron Giulia,
Ermondi Giuseppe,
Fruttero Roberta
Publication year - 2001
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/1522-2675(20010228)84:2<375::aid-hlca375>3.0.co;2-4
Subject(s) - chemistry , cetirizine , lipophilicity , hydroxyzine , intramolecular force , partition coefficient , stereochemistry , organic chemistry , immunology , biology , medicine , pharmacology
A recent analysis of the lipophilicity profile of cetirizine in the octanol/water and dodecane/water systems revealed a partial intramolecular charge neutralization that can partly explain why cetirizine has pharmacokinetic properties differing from those of first‐generation antihistamines such as hydroxyzine. As conformational changes are the principal driving force for this intramolecular effect, the present study deals with the partitioning of cetirizine and hydroxyzine in an apolar medium well‐suited to reveal intramolecular interactions, namely the 1,2‐dichloroethane/water system. The lipophilicity of the different electrical forms of cetirizine and hydroxyzine was studied by two‐phase titrimetry and cyclic voltammetry. The differences in lipophilicity between the dicationic, monocationic, zwitterionic, and anionic species of cetirizine indicated intramolecular interactions via folded conformations, which render the molecule markedly more lipophilic than expected at physiological pH. Folded conformations were also found to predominate in monocationic and neutral hydroxyzine. The ionic partition diagram of cetirizine indicates that it acts as a proton transporter across interfaces under certain conditions of pH and Galvani potential difference. This study underlines the importance of conformational effects on the partition properties of cetirizine and hydroxyzine, as well as the complexity of its interfacial mechanisms of transfer. In particular, cetirizine can facilitate proton transfer, a property of potential biological relevance.