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J Asthma. 1996;33(6):417-23.
The effect of cetirizine on the integrin-dependent respiratory burst of normodense eosinophils.

Piacentini GL, Mazzi P, Vinco S, Peroni DG, Ferro I, Vicentini L, Boner AL.

Clinica Pediatrica Universita di Verona, Italy.

It has been proposed that cetirizine inhibits eosinophil migration and adherence. We evaluated the possible effect of cetirizine on integrin-induced eosinophil proinflammatory activation. Normodense eosinophils were triggered with monoclonal antibodies to integrins in the presence of different concentrations of certirizine. Proinflammatory activation was measured by evaluation of O2- production. Only at high concentrations (250 micrograms/ml) and in the first 15 min did certirizine significantly inhibit (p < 0.02) the eosinophil respiratory burst. No effect was shown for lower concentrations (50 and 100 micrograms/ml) or after 15 min. These data suggest that, only at very high concentrations, cetirizine may induce a transient inhibition of the integrin-induced eosinophil respiratory burst.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8968296&dopt=Abstract

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Ann Allergy Asthma Immunol. 1997 Feb;78(2):183-6.
Prospective controlled study of hydroxyzine and cetirizine in pregnancy.

Einarson A, Bailey B, Jung G, Spizzirri D, Baillie M, Koren G.

Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada.

BACKGROUND: Hydroxyzine has been used for many years for the treatment of allergic symptoms. Cetirizine, an active metabolite of hydroxyzine, has become very popular for the treatment of allergy symptoms because of its efficacy without the sedating effects of the parent compound. Little is known about the safety of hydroxyzine use during pregnancy, and there are no published reports on the effects of cetirizine on pregnancy outcome. OBJECTIVE: To determine whether hydroxyzine and cetirizine are associated with any increased risk of malformations in humans. METHODS: All pregnant women counseled by the Motherisk Program in Toronto on the use of hydroxyzine or cetirizine during their pregnancies were enrolled in a prospective, controlled, observational study. The control group consisted of pregnant women matched for age, smoking, and alcohol consumption who were counseled for non-teratogenic drug. RESULTS: One hundred twenty women were followed after exposure to either hydroxyzine or cetirizine during pregnancy. Of these, 53 were exposed to hydroxyzine during organogenesis and 39 to cetirizine. There were no significant differences found between the hydroxyzine or cetirizine groups and the control groups in the pregnancy outcome: rate of livebirths, spontaneous or therapeutic abortion, or stillbirth. There was also no difference in the rates of major or minor anomalies, mean birth weight, mode of delivery, gestational age, or presence of neonatal distress. CONCLUSIONS: The use of hydroxyzine and cetirizine does not appear to be associated with increased teratogenic risk.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9048526&dopt=Abstract

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Am J Vet Res. 1997 Mar;58(3):293-7.
Effect of H1-antihistamines on histamine release from dispersed canine cutaneous mast cells.

Garcia G, DeMora F, Ferrer L, Puigdemont A.

Department de Farmacologia i Terapeutica, Universitat Autonoma de Barcelona, Bellaterra, Spain.

OBJECTIVE: Because of the implication of histamine in canine atopic dermatitis, H1-antihistamines may provide a valid alternative to glucocorticoid therapy. In vitro study of these drugs prior to clinical testing can allow the most promising compounds to be selected for trials and render trials with drugs of doubtful efficacy unnecessary. SAMPLE POPULATION: Isolated canine cutaneous mast cells. PROCEDURE: Cells were preincubated with antihistamines at increasing concentrations and incubated with concanavalin A (1,000 micrograms/ml), calcium ionophore A23187 (1 microM), and substance P (100 microM). Compound 48/80 was not used because it proved to be cytotoxic. RESULTS: Generally, significant prodegranulating effect was not observed for most of the studied agents. Only terfenadine increased spontaneous histamine release at concentrations > 30 microM. Cetirizine did not block histamine release at any of the studied concentrations. Ketotifen had a low inhibitory effect only at the highest concentration (100 microM) after concanavalin A- (23.6 +/- 2.8%) and calcium ionophore A23187- (29.8 +/- 3.0%) induced release. Terfenadine caused a concentration-dependent inhibitory effect after ionophore A23187- (48.1 +/- 2.2%) and concanavalin A- (28.9 +/- 2.3%) activation, but was inactive against substance P-induced release. In contrast, loratadine had potent dose-dependent inhibition of concanavalin A- and ionophore A23187-induced histamine release, with maximal effect of 85.6 +/- 3.1% and 62.6 +/- 4.7%, respectively, at 100 microM concentration. After substance P activation, histamine release was only slightly inhibited by loratadine (14.8 +/- 1.1%). CONCLUSIONS: This study documents the behavior of isolated canine cutaneous mast cells in the presence of nonimmunologic stimulation. Using this in vitro method, we were able to determine that loratadine is the only antihistamine that has potent inhibition of histamine release from dog cutaneous mast cells without a substantial prodegranulating effect. Loratadine is, therefore, a good candidate for clinical testing.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9055977&dopt=Abstract

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