title: Triprotic acid-base microequilibria and pharmacokinetic sequelae of cetirizine.
abstract: (1)H NMR-pH titrations of cetirizine, the widely used antihistamine and four related compounds were carried out and the related 11 macroscopic protonation constants were determined. The interactivity parameter between the two piperazine amine groups was obtained from two symmetric piperazine derivatives. Combining these two types of datasets, all the 12 microconstants and derived tautomeric constants of cetirizine were calculated. Upon this basis, the conflicting literature data of cetirizine microspeciation were clarified, and the pharmacokinetic absorption-distribution properties could be interpreted. The pH-dependent distribution of the microspecies is provided.
authors.affiliation: Department of Pharmaceutical Chemistry, Semmelweis University, Research Group of Drugs of Abuse and Doping Agents, Hungarian Academy of Sciences, Budapest H-1092, Hogyes Endre u. 9, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Marosi
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Kovács
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Béni
authors.forename: József
authors.initials: J
authors.lastname: Kökösi
authors.forename: Béla
authors.initials: B
authors.lastname: Noszál
mesh_terms: D000143:Acids / Q000737:chemistry; D000465:Algorithms; D000468:Alkalies / Q000737:chemistry; D017332:Cetirizine / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D006919:Hydroxyzine / Q000737:chemistry / Q000493:pharmacokinetics; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D010879:Piperazines / Q000737:chemistry; D011522:Protons
chemical_list: D000143:Acids; D000468:Alkalies; D006634:Histamine H1 Antagonists; D007202:Indicators and Reagents; D010879:Piperazines; D011522:Protons; D006919:Hydroxyzine; D017332:Cetirizine