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The effects of astemizole, cetirizine and loratadine on the time course of weal and flare reactions to histamine, codeine and antigen.

Humphreys F, Hunter JA.

University Department of Dermatology, Royal Infirmary, Edinburgh, U.K.

An open cross-over study was performed to assess the effects of astemizole, cetirizine and loratadine on weal and flare reactions to intradermal histamine, codeine and house dust mite antigen. Percentage inhibition of weal area, flare area and weal volume was greatest for cetirizine, then astemizole and smallest for loratadine. Wealing due to mast-cell degranulation with either codeine or antigen was less inhibited by all three antihistamines than that due to histamine itself. Time-course studies revealed similarities between wealing provoked by codeine and histamine but different characteristics to that induced by antigen.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1683252&dopt=Abstract cetirizine Zyrtec



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Platelet-activating factor-induced immediate and late cutaneous reactions.

Rihoux JP, Fadel R, Juhlin L.

UCB SA, Belgium.

In atopic subjects, intradermal injection of platelet-activating factor (PAF), 40 and 400 ng, resulted in an immediate edema reaction markedly blocked by cetirizine, 10 mg twice a day. PAF challenge also induced a significant eosinophil accumulation evidenced by a skin window technique at 2, 4, 8 and 24 h. This inflammatory phenomenon was significantly inhibited by cetirizine. In patients with chronic urticaria, PAF, 100 micrograms intradermally, induced immediate and late cutaneous reactions (LCR) also blocked by cetirizine, 10 mg twice a day. These LCR were accompanied by an infiltration of the deep dermis by degranulated eosinophils. The pathophysiological mechanism of the PAF-induced skin reactions is discussed as well as the mechanism of action of cetirizine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1834582&dopt=Abstract cetirizine Zyrtec



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Effect of cetirizine on cutaneous reactions to PAF, kallikrein and serum in patients with chronic urticaria.

Juhlin L, Rihoux JP.

Department of Dermatology, University Hospital, Uppsala, Sweden.

The effects of oral administration of the antihistamine cetirizine on the weal and flare caused by intradermal injection of platelet activating factor (PAF-acether), kallikrein, histamine and the patient's own serum were investigated in 10 patients with chronic urticaria. Cetirizine markedly reduced the weal and flare induced by all these agents as measured 12 min after the injections. The delayed reactions observed after injection of PAF, kallikrein and serum were also inhibited by cetirizine at 6 hours. In addition, reactions which were present 20 h after injection of the agent before administration of cetirizine were found to be inhibited at the same point in time after cetirizine treatment. These effects might explain the good inhibitory clinical effect of cetirizine on the patients' urticaria. No side-effects were noted during the treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1969202&dopt=Abstract cetirizine Zyrtec



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Effect of haemodialysis on the pharmacokinetics of cetirizine.

Awni WM, Yeh J, Halstenson CE, Opsahl JA, Chung M, Matzke GR.

Drug Evaluation Unit, Hennepin County Medical Center, Minneapolis, Minnesota.

The pharmacokinetics of Cetirizine, a histamine H1-receptor antagonist, were investigated in five renal failure patients undergoing chronic haemodialysis therapy. The patients received one 10 mg cetirizine dihydrochloride capsule 3 h before haemodialysis. Concentrations of cetirizine in serum and dialysate were determined by HPLC. The maximum serum cetirizine concentration and the time to reach that maximum were 285 micrograms.l-1 and 2.0 h, respectively. The terminal disposition half-life of cetirizine in these patients was 19.3 h. The haemodialysis clearance of cetirizine was 14.0 ml. min-1. Although this is approximately 33% of the apparent total body clearance of cetirizine in subjects with normal renal function, the fraction of the dose removed by dialysis was only 9.4%. Thus, since haemodialysis does not produce a clinically significantly alteration in cetirizine elimination, no supplemental dose should be necessary after dialysis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1970299&dopt=Abstract cetirizine Zyrtec



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Cetirizine: actions on neurotransmitter receptors.

Snowman AM, Snyder SH.

Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2105.

First-generation H1-antagonist antihistamines, such as hydroxyzine, have the ability to cross the blood-brain barrier and cause sedation, which limits their usefulness in the treatment of allergic disorders. Cetirizine, a carboxylated metabolite of hydroxyzine, possesses the parent compound's antihistaminic activity but causes less sedation. We compared the activity of cetirizine at central H1 sites with that of hydroxyzine and terfenadine. We also compared the ability of cetirizine and three antihistamines to cross the blood-brain barrier. In each case we found that the drug's potency at H1 receptors in the central nervous system was similar to its activity in displacing H1 receptors in the lung. However, the selectivity for H1 receptors varied widely from drug to drug. Cetirizine did not bind at any of the receptors investigated, except H1 sites, even at concentrations as high as 10 mumol/L. Hydroxyzine and dexchlorpheniramine and, to a lesser extent, terfenadine crossed the blood-brain barrier in significant amounts. Cetirizine passed into the central nervous system only half as readily as terfenadine. These findings suggest that cetirizine's low incidence of sedative effects is most likely caused by its diminished potential to cross the blood-brain barrier and also may be partly the result of its greater selectivity for H1 receptors, compared with its effect at other receptors that may be involved in sedation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1979798&dopt=Abstract cetirizine Zyrtec



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Cetirizine counter-regulates interleukin-8 release from human epithelial cells (A549)

Arnold R, Rihoux J, Konig W.

Institute of Medical Microbiology and Immunology, AG Infektabwehr, Ruhr-University, Bochum, Germany; Institute of Medical Immunology, Charite-Campus Mitte, Humboldt University, Berlin, Germany.

BACKGROUND: Cetirizine, a H1-receptor antagonist, exerts besides its well-known anti-allergic potential an array of anti-inflammatory activities. In particular epithelial cells activated in the presence of cetirizine showed a reduced ICAM-1 cell surface expression and a diminished release of sICAM-1. OBJECTIVE: We wondered whether cetirizine might influence the release of interleukin-8 (IL-8) from human epithelial cells activated with agonists distinct from histamine. METHODS: We used the human lung epithelial cell line A549 for our in vitro studies. IL-8 release was determined by IL-8 enzyme immunoassay, the intracellular staining for IL-8 and NF-kB was analysed by FACS analysis and IL-8 mRNA steady state level was studied by Northern blot analysis. Confluent epithelial cell monolayer were pre-incubated with cetirizine (0.01 -1.0 micromol/L) for 30 min and afterwards activated with pro-inflammatory cytokines (TNF-alpha IL-1beta, IL-6, IFN-gamma) or different agonists (PMA, NaF, respiratory syncytial virus [RSV]) for 24 h. RESULTS: Epithelial cells stimulated with TNF-alpha IL-1beta, PMA and RSV, respectively, showed a significantly increased release of IL-8. Pre-incubation with cetirizine diminished the IL-8 release from cells activated with TNF-alpha or PMA in a significant manner. The reduced IL-8 release coincided with a diminished percentage of cells expressing IL-8. Northern blot analysis revealed a reduced steady state level of IL-8 mRNA in cells pretreated with cetirizine and stimulated with TNF-alpha. Furthermore, a decreased amount of accessible DNA-binding sites of the nuclear factor kappa B (NF-kB) was determined by FACS analysis. CONCLUSIONS: These results suggest that cetirizine reduced the release of IL-8 from A549 cells stimulated with PMA and TNF-alpha, respectively, by lowering IL-8 gene expression. Therefore, cetirizine might exert anti-inflammatory effects beyond its H1-receptor antagonistic activity in the course of inflammatory respiratory tract disorders such as bronchial asthma and allergic rhinitis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10594545&dopt=Abstract cetirizine Zyrtec