Disease relevance of Levocetirizine

• Adults with persistent rhinitis sensitized to both grass pollen and house dust mite were randomized to receive levocetirizine 5 mg/d or placebo [1].
• Levocetirizine (Xyzal) is a selective, potent, oral histamine H(1) receptor antagonist of the latest generation that is licensed for the symptomatic treatment of allergic rhinitis (including persistent allergic rhinitis [PER]) and chronic idiopathic urticaria (CIU) [2].
• This paper aims to review the pathophysiologic background of nasal obstruction and the evidence for an antihistamine, levocetirizine, in relieving nasal congestion [3].
• OBJECTIVE: The aim of this pilot study was to evaluate nasal symptoms, nasal airflow, inflammatory cells, and cytokine pattern in patients with seasonal allergic rhinitis (SAR), before and after treatment with levocetirizine, desloratadine, or placebo [4].
• Levocetirizine decreased the size of wheals by 60% (p < 0.001) and accompanying pruritus by 62% (p < 0.001) compared with placebo [5].

Psychiatry related information on Levocetirizine

• Acute and subchronic effects of levocetirizine and diphenhydramine on memory functioning, psychomotor performance, and mood [6].
• CONCLUSIONS: This study showed that levocetirizine does not produce any deleterious effect on cognitive and psychometric functions compared with placebo in healthy male volunteers [7].

High impact information on Levocetirizine

• Levocetirizine has pharmacodynamically and pharmacokinetically favourable characteristics, including high bioavailability, rapid onset of action, limited distribution and a low degree of metabolism [8].
• Levocetirizine: pharmacokinetics and pharmacodynamics in children age 6 to 11 years [9].
• RESULTS: In children aged 8.6 +/- 0.4 years (+/- SEM), the peak levocetirizine concentration was 450 +/- 37 ng/mL, and the time at which peak concentrations occurred was 1.2 +/- 0.2 hours [9].
• Levocetirizine improves quality of life and reduces costs in long-term management of persistent allergic rhinitis [1].
• Binding kinetics provided a suitable explanation for this observation, because levocetirizine dissociated from H(1) receptors with a half-time of 142 min; that of (S)-cetirizine was only 6 min, implying that the former could act as a pseudo-irreversible antagonist in functional studies [10].

Chemical compound and disease context of Levocetirizine

• OBJECTIVE: We sought to investigate the effects of levocetirizine (5 mg), diphenhydramine (50 mg), and placebo on memory and psychomotor performance after acute (day 1) and subchronic (day 4) daily administration in 48 healthy volunteers (24 men and 24 women) [6].
• A meta-analysis on the early and late effects of levocetirizine on nasal obstruction under artificial and natural allergen exposure conditions is presented, demonstrating convincingly that levocetirizine shows a consistent effect on nasal obstruction as early as over the first 2 h and sustained over 6 weeks [3].
• Comparative efficacy of cetirizine and levocetirizine in chronic idiopathic urticaria [11].

Biological context of Levocetirizine

• For patients with allergic rhinitis without asthma/wheezing, the sex-adjusted odds of drowsiness/sedation were over six times greater in patients using levocetirizine than desloratadine in the first month of observation, with the OR being statistically significant [12].
• All the patients received levocetirizine (5 mg.day) for 4 weeks, and the speed of nasal mucociliary clearance was assessed before and after treatment [13].
• A direct comparison of the efficacy of antihistamines in SAR and PAR: randomised, placebo-controlled studies with levocetirizine and loratadine using an environmental exposure unit - the Vienna Challenge Chamber (VCC) [14].
• The protein binding of radiolabelled levocetirizine was 96.1% l h after administration [15].
• Moreover the non-renal clearance of levocetirizine is also significantly lower than that of the distomer (9.70 and 28.70 mL/min, respectively), which constitutes an additional positive aspect particularly as far as metabolism-based drug interactions are concerned [16].

Anatomical context of Levocetirizine

• Levocetirizine almost abolished resting eosinophil adhesion by the 15 min time-point [17].
• BACKGROUND: We previously demonstrated that low concentrations of a new antihistamine levocetirizine inhibited eosinophil transmigration through human microvascular endothelial cells [17].
• Levocetirizine significantly reduced eosinophils (P=0.029), neutrophils (P=0.005), IL-4 (P=0.041), and IL-8 (P=0.02), whereas desloratadine diminished IL-4 only (P=0.044) [4].
• OBJECTIVE: Here, the inhibitory effect of levocetirizine on eosinophil adhesion to recombinant human vascular cell adhesion molecule-1 (rhVCAM)-1 was examined under conditions of shear stress using an in vitro model of the post-capillary venules [17].
• Levocetirizine and/or its metabolites were not, or only very poorly, associated with blood cells, as the blood-to-plasma ratio was 0.51 to 0.68 [15].

Associations of Levocetirizine with other chemical compounds

• Furthermore, no effect on spontaneous eosinophil TEM, or eosinophil viability was seen with any concentration of cetirizine or levocetirizine [18].
• METHODS: Levocetirizine (5 mg), loratadine (10 mg), or placebo was taken orally 4 h before the intradermal injection of histamine (20 microl, 100 microM) or the control vehicle into the forearm skin of healthy volunteers [19].
• At 24 h it was significantly more pronounced after levocetirizine than fexofenadine (difference: least-squares mean: -0.13 degrees C; P < or = 0.024, 95% CI -0.24, -0.02) [20].
• We found that the magnitude of the pH effect on the dissociation rate of levocetirizine was maintained after mutating Lys191 into alanine, suggesting that a tighter interaction of levocetirizine with Lys191 at lower pH is not the cause of its even slower dissociation rate from the receptor [21].
• Second-generation H1 receptor antagonists such as desloratadine, levocetirizine and ebastine provide good selective H1 receptor blockade without anticholinergic or alpha-adrenoceptor antagonist activity [22].

Gene context of Levocetirizine

• Objectives To determine if 6 weeks of therapy with levocetirizine 5 mg once daily would also induce any decrease in serum levels of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, endothelial leucocyte adhesion molecule-1 (ELAM-1) or P-selectin in subjects with CU and chronic autoimmune urticaria [23].
• The fact that levocetirizine is a substrate of P-gp, although weak in an in vitro model, could contribute to prevent drug penetration into the brain, whereas it is unlikely to be of any clinical relevance for P-gp-mediated drug interactions [24].
• CONCLUSION: Physiologically relevant concentrations of levocetirizine inhibit resting and GM-CSF-stimulated firm eosinophil adhesion to rhVCAM-1 under flow conditions [17].
• Cetirizine and levocetirizine inhibit eotaxin-induced eosinophil transendothelial migration through human dermal or lung microvascular endothelial cells [18].
• We evaluated single and short-term dosing effects of a modern histamine H1-receptor antagonist, levocetirizine, given at the usual clinically recommended dose, on the primary outcome of AMP bronchoprovocation [25].

Analytical, diagnostic and therapeutic context of Levocetirizine

• OBJECTIVE: We sought to compare levocetirizine and desloratadine in a nasal provocation test (NPT) with grass pollen [26].
• Treatment cessation because of lack of effect, comorbidities, and overall costs of disease, and comorbidities per working patient per month (160.27 vs 108.18) were lower in the levocetirizine group [1].
• Pathophysiology of nasal obstruction and meta-analysis of early and late effects of levocetirizine [3].
• METHODS: A total of 294 patients with PAR due to house dust mites were randomized in this 8-week double-blind, placebo-controlled, multicentre trial to receive either levocetirizine 5 mg/day or placebo [27].
• METHODS: This was a randomized, double-blind, three-treatment, three-period, single-dose, cross-over study in healthy males taking levocetirizine 5 mg, fexofenadine 120 mg or placebo [20].

References