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Suppression by cetirizine of pleurisy triggered by antigen in actively sensitized rats.

Pasquale CP, e Silva PM, Lima MC, Diaz BL, Rihoux JP, Vargaftig BB, Cordeiro RS, Martins MA.

Fundacao Oswaldo Cruz, Departamento de Fisiologia e Farmacodinamica, Rio de Janeiro, Brazil.

The efficacy of cetirizine in comparison with meclizine, another piperazine H1 receptor antagonist, in rat pleurisy caused by allergen or autacoid was investigated. Sensitization was achieved by subcutaneous injection of a mixture of ovalbumin and aluminium hydroxide. Fourteen days later, the animals were challenged with an intrathoracic injection of ovalbumin (12 micrograms/cavity), which caused drastic mast cell degranulation, followed by pleural oedema and leucocyte influx. Cetirizine and meclizine (2.5-30 mg/kg i.p.), 1 h before challenge, inhibited the exudatory response evoked by antigen, under conditions where neutrophil and eosinophil accumulation was affected only by the former. When administered intrathoracically 22 h after allergen, i.e. using a curative approach, cetirizine (15 micrograms/cavity) drastically reduced the pleural eosinophilia noted 24 h post-challenge, indicating that this drug can reverse an already established eosinophilia. Cetirizine (15 mg/kg i.p.) also restored, to about 39% (P < 0.001), the number of uninjured mast cells recovered from the pleural cavity following allergen stimulation. In normal rats, cetirizine (5-15 micrograms/cavity) completely inhibited the pleural exudation elicited by histamine and only partially the exudation caused by 5-hydroxytryptamine or bradykinin, but was quite inactive against platelet-activating factor. We conclude that the pleural exudation triggered by allergen, vasoactive amines or bradykinin is clearly sensitive to cetirizine. In addition, the ability of the drug to interfere with pleural neutrophil or eosinophil mobilization and mast cell degranulation seems not to be associated with its ability to block the histamine H1 receptor.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1362160&dopt=Abstract cetirizine Zyrtec



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Cetirizine: a unique second-generation antihistamine for treatment of rhinitis and chronic urticaria.

Pierson WE.

Department of Pediatrics, University of Washington, Seattle.

The recent development of selective H1-antagonists that minimally cross the blood-brain barrier has greatly improved the management of allergic rhinitis and chronic urticaria. These new agents have much reduced anticholinergic and sedative side effects, which were the major drawbacks of the classic H1-antihistamines. Cetirizine, a new second-generation H1-antagonist, offers several properties that may further improve the treatment of allergic rhinitis and chronic urticaria. Cetirizine is the only antihistamine known to possess activity against both the histamine-mediated early phase of the allergic response and the late-phase response of immediate hypersensitivity characterized by migration of inflammatory cells to the site of the reaction. Its efficacy has been demonstrated in clinical trials of patients with seasonal rhinitis and urticaria. The most common side effects associated with cetirizine, such as sedation, are similar to those of other second-generation antihistamines. These properties, combined with a once-daily dosage regimen, should help improve patient compliance and optimize antihistamine therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1674232&dopt=Abstract cetirizine Zyrtec



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[Non-sedative antihistaminics and binding to central and peripheral H1 histamine receptors]

[Article in French]

Leysen JE, Gommeren W, Janssen PF, Sanz G, Gillardin JM, Schotte A, Janssen PA.

Janssen Research Foundation, Beerse, Belgique.

Four non-sedating antihistamines (astemizole, cetirizine, loratadine and terfenadine) were investigated for in vitro and ex vivo binding to histamine-H1 receptors in guinea-pig cerebellum and lung. In vitro, all the drugs dissociated slowly from H1 receptors (half-times greater than or equal to 100 min), Ki,app-values decreased with longer incubation times for potent lipophylic agents (astemizole and terfenadine) Ki,app-values were lower with more dilute tissue suspensions. In optimized assay conditions astemizole showed a Ki,app-value of 0.2 microM. Terfenadine, cetirizine and loratadine bound with 30-, 80- and 100-times lower affinity to H1 receptors. The occupancy of lung and cerebellar H1 receptors was investigated after oral administration of various dosages of the drugs and at several times after drug administration, using ex vivo binding techniques. Astemizole was a very potent compound showing complete differentiation between lung and cerebellar receptor occupation (with 0.63 mg/kg: 70% of lung H1 receptors were occupied, with less than 10% of cerebellar H1 receptor occupancy). A 7-times higher dose of terfenadine was required to induce the same effect. Astemizole produced a rapid and complete occupancy of lung receptors, which was maintained up to 72 h after administration. In contrast, terfenadine produced a peak effect at 1 h and was completely eliminated from lung receptors in 24 h. Loratadine and cetirizine only poorly differentiated between lung and cerebellar receptor occupancy (at 2.5 mg/kg: 70 and 60% of lung receptor occupancy, 50 and 70% of cerebellar receptor occupancy).(ABSTRACT TRUNCATED AT 250 WORDS)

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1677249&dopt=Abstract cetirizine Zyrtec



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Determination of cetirizine in human urine by high-performance liquid chromatography.

Rosseel MT, Lefebvre RA.

Heymans Institute of Pharmacology, University of Ghent Medical School, Belgium.

A high-performance liquid chromatographic method for the determination of the histamine H1-receptor antagonist cetirizine in human urine was developed. Cetirizine and the internal standard are extracted from acidified (pH 5) urine (0.5 ml) into chloroform and the organic layer is evaporated to dryness. The residue is chromatographed on a Spherisorb 5ODS-2 column using Pic A (5 mM aqueous tetrabutylammonium phosphate)-methanol-tetrahydrofuran (33:65:2, v/v) as the mobile phase with ultraviolet detection (230 nm). The calibration graph is linear from 0.1 to 10 micrograms/ml and using 0.5 ml of urine the detection limit is 20 ng/ml. The within-run relative standard deviation is less than 6% and the accuracy is within 10% of the theoretical value at concentrations between 0.1 and 10 micrograms/ml in urine. There is a good correlation (r = 0.99606) with a previously described capillary gas chromatographic assay.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1678748&dopt=Abstract cetirizine Zyrtec



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The effect of cetirizine on antigen-dependent leucopenia in the guinea-pig.

Coyle AJ, Lefort J, Vargaftig BB.

Unite de Pharmacologie Cellulaire, INSERM No. 285, Paris, France.

1. Intravenous administration of ovalbumin (1 mg kg-1) to guinea-pigs that had previously been injected with 3.5 x 10(9) platelets from actively sensitized animals induced an approximately 40% decrease in the number of circulating leucocytes 30-60 min later, whereas the number of platelets was not affected. 2. In contrast, there was no change in the leucocyte number following antigen challenge of guinea-pigs that had received platelets from non-immunised animals. 3. This platelet-dependent leucopenia was inhibited by prior treatment of the recipient animal with cetirizine (10-30 mg kg-1, i.v.). Terfenadine (50 mg kg-1, p.o.) and mepyramine (2 mg kg-1, i.v.) were completely inactive in this respect. All doses of anti-histamines were used at concentrations which completely inhibited the bronchoconstriction to an i.v. injection of 5 micrograms kg-1 of histamine. 4. The site of action of cetirizine is most likely to be the platelet as leucopenia induced by the neutrophil agonists leukotriene B4 (LTB4) (30 ng kg-1) and platelet activating factor (PAF) (30 ng kg-1) were not modified by cetirizine treatment. 5. In these experiments, we failed to support a role for lipoxygenase products as mediators of the platelet-dependent leucopenia, as the selective lipoxygenase inhibitor BWA4C (50 mg kg-1, p.o.) was ineffective. 6. Our present results confirm and extend previous data demonstrating that antigen stimulated platelets can induce leucopenia in non-immunised animals and this can be inhibited by the anti-allergic agent, cetirizine, by an action which is probably unrelated to its anti-histamine properties.(ABSTRACT TRUNCATED AT 250 WORDS)

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1679361&dopt=Abstract cetirizine Zyrtec



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Effects of cetirizine on human eosinophil and neutrophil activation in vitro.

Walsh GM, Moqbel R, Hartnell A, Kay AB.

Department of Allergy and Clinical Immunology, National Heart and Lung Institute, London, UK.

The ability of cetirizine, a novel antihistamine agent, to inhibit the in vivo activation of human eosinophils, neutrophils and monocytes has been investigated using C3b- and IgG-dependent rosette formation, cytotoxicity against opsonised parasitic larvae and adherence to plasma-coated glass (PCG). The drug inhibited platelet-activating factor (PAF)-induced enhancement of eosinophil and neutrophil IgG (Fc) and complement (C3b) rosettes with an IC50 of 2 x 10(-5) M. There was also comparable inhibition of PAF-dependent enhancement of eosinophil cytotoxicity (for complement-coated schistosomula of Schistosoma mansoni). Cetirizine inhibited PAF-induced eosinophil, but not neutrophil, hyperadherence to PCG. These data support the view that cetirizine may exert some of its anti-allergic effects by inhibiting the activation of human granulocytes and that it may also selectively inhibit PAF-induced eosinophil hyperadherence.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1682275&dopt=Abstract cetirizine Zyrtec