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RP-LC method for the determination of cetirizine in serum.

Zaater MF, Tahboub YR, Najib NM.

Department of Applied Chemical Sciences, Faculty of Science, Jordan University of Science and Technology, Irbid. mzaater usa.net

The development and evaluation of HPLC method for quantifying cetirizine in human serum is described. The method involves liquid phase extraction of cetirizine in methylene chloride, adding diazepam as an internal standard, followed by separation on a reversed phase C18 Novapak column (150 x 3.9 nm; 4 microm), and employing a UV-detection set at 230 nm at ambient temperature. The mobile phase consists of a 13 mM phosphoric acid solution and acetonitrile (61:39 v/v) adjusted to pH 2.8 with 5 M NaOH. The assay is linear from 10 to 500 ng ml(-1) with a detection limit of 5 ng ml(-1) and a mean recovery of 96.5%. The applicability of this method in pharmacokinetic studies is evaluated.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10815716&dopt=Abstract cetirizine Zyrtec



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Effect of cetirizine on antigen-induced tracheal contraction of passively sensitized guinea pigs.

Dobashi K, Iizuka K, Houjou S, Sakai H, Watanabe K, Mori M, Nakazawa T.

First Department of Internal Medicine, Gunma University, School of Medicine, Japan.

BACKGROUND: Cetirizine dihydrochloride (cetirizine), a potent histamine H1-receptor antagonist, has been developed as an anti-allergy drug. OBJECT: The anti-allergic effects and mechanism of cetirizine were studied using in vitro assay systems. METHODS: We investigated the effect of cetirizine on antigen-induced contractions of isolated tracheal strips and on chemical mediator release from antigen-stimulated lung chips taken from passively sensitized guinea pigs. We examined the antigen-induced mobilization of Ca2+ in MC/9 mast cells sensitized with IgE. RESULTS: Cetirizine inhibited the antigen-induced contraction of isolated guinea-pig trachea concentration dependently. Pyrilamine, another histamine H1-receptor antagonist, delayed the response but did not change the maximum amplitude. Cetirizine at the concentration of 3 microM also inhibited the antigen-induced release of histamine, leukotriene D4, and leukotriene E4 from guinea pig lung chips. Furthermore, it inhibited the antigen-induced Ca2+ increase in MC/9 mast cells, whereas pyrilamine did not. CONCLUSION: These findings suggest that one anti-allergic mechanism of cetirizine may inhibit mediator release which is, at least partially, mediated by a decrease in the transient Ca2+ influx in mast cells.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8885809&dopt=Abstract cetirizine Zyrtec



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Predictors of torsades de pointes in rabbit ventricles perfused with sedating and nonsedating histamine H1-receptor antagonists.

Gilbert JD, Cahill SA, McCartney DG, Lukas A, Gross GJ.

Department of Paediatrics and Child Health, University of Manitoba, Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Canada.

Several nonsedating histamine H1-receptor antagonists are associated with torsades de pointes ventricular tachycardia. The objectives of this study were to: (i) compare electrocardiographic, monophasic action potential, and arrhythmogenic effects of sedating and nonsedating H1-receptor antagonists, and (ii) identify correlates of drug-induced torsades de pointes in an isolated ventricle model. Isolated, electrically paced (1-3 Hz) rabbit ventricles were Langendorff-perfused with either drug-free Tyrode's solution or one of the following: (i) the sedating H1-receptor antagonist hydroxyzine (0.1-30 microM), (ii) cetirizine, a nonsedating metabolite of hydroxyzine (1-300 microM), and (iii) the nonsedating, putatively arrhythmogenic H1-receptor antagonist astemizole (0.1-30 microM). Volume conducted electrocardiographic signals and monophasic action potentials from the periapical left ventricular endocardium and epicardium were recorded. There were no apparent changes in control (n = 15) or hydroxyzine-perfused (n = 7) hearts. Cetirizine (n = 13) produced a mild biphasic electrocardiographic QT interval prolongation and was associated with early afterdepolarizations, but not with torsades de pointes. Astemizole (n = 11) lengthened QT intervals, and at high concentration (30 microM) induced torsades de pointes in 10 of 11 hearts (P < 0.001 vs. all other groups). These findings are consistent with previously reported repolarizing current inhibition by cetirizine, but may additionally indicate "compensatory" inhibition of inward currents at higher concentrations. By contrast, astemizole-induced changes are consistent with unopposed repolarizing current inhibition.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10841436&dopt=Abstract cetirizine Zyrtec



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



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



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Pharmacokinetics and pharmacodynamics of cetirizine in infants and toddlers.

Spicak V, Dab I, Hulhoven R, Desager JP, Klanova M, de Longueville M, Harvengt C.

Hospital Bulovka, Prague.

The pharmacokinetics of the second generation H1-receptor antagonist cetirizine were studied in 15 infants and toddlers (mean +/- SD age, 12.3 +/- 5.4 months) who were treated with a single 0.25 mg/kg dose of cetirizine solution. The infants and toddlers were hospitalized for recurrent respiratory infections or other hypersensitivity-related diseases. Blood samples were collected at 1/2, 1, 11/2, 2, 4, 6, 8, 12, and 24 hours, and a 24-hour urine sample was obtained. A peak plasma level of 390 +/- 135 ng/ml was observed after 2.0 +/- 1.3 hours. The elimination half-life was 3.1 +/- 1.8 hours, the apparent oral body clearance was 2.13 +/- 1.15 ml/min/kg, and the apparent volume of distribution was 0.44 +/- 0.19 L/kg. The excretion of unchanged cetirizine in six complete urinary collections was 62.7% +/- 13.2% of the administered dose. An additional pharmacodynamic study (inhibition of the histamine-induced wheal and flare) was performed in 10 of these infants and toddlers, after the intake of 0.25 mg/kg cetirizine twice a day for at least 4 days. A 90% +/- 12% inhibition of the wheal and a 87% +/- 17% inhibition of the flare were still observed 12 hours after the last intake. The duration of the H1-inhibition by cetirizine at the cutaneous level is thus longer in infants and toddlers than could be inferred from its pharmacokinetics; the level of inhibition at 12 hours was the same as in older age groups.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9084458&dopt=Abstract cetirizine Zyrtec