Physicochemical, Pharmacological and Pharmacokinetic Properties of the Zwitterionic Antihistamines Cetirizine and Levocetirizine

摘要: Cetirizine, marketed as a racemic mixture containing both levocetirizine and dextrocetirizine, is member of the second generation H(1) antihistamines clinically used for treatment symptoms associated with seasonal allergic rhinitis. Recently, its single R-enantiomer has been approved by FDA newest antihistamine. Cetirizine piperazine derivative related to first antagonist hydroxyzine, major metabolite in blood circulation after hydroxyzine administration humans. The acid functionality cetirizine combination one basic nitrogens ring makes this compound very unique zwitterion. molecular structure allows carboxylic group interact nitrogen via folded conformers, therefore, it possesses relatively high lipophilicity at physiological pH (LogD=1.5). While possess affinity receptor, R-configured much slower dissociation rate from receptor than R-hydroxyzine, making an insurmountable antagonist. In addition, pharmacokinetics significantly differs those lipophilic hydroxyzine. For example, lower CNS penetration which may be explained zwitterionic P-glycoprotein activity. exhibits intestinal absorption humans oral bioavailability estimated greater 70%. Very importantly, cetirizine, especially levocetirizine, negligible interaction liver enzymes, mainly excreted urine parent despite plasma protein binding (88 approximately 96%). recommended dose 5 mg once daily, while pharmacokinetic half-life about 7 h This review will focus on physicochemical, pharmacological properties comparison displays distinct advantages over several categories such slow rate, selectivity, enzyme low penetration. Therefore, or isomer might serve good example medicinal chemists design drugs basic, acidic neutral lead molecule peripheral biological targets.