Zyrtec
Effects of cetirizine dihydrochloride on human lymphocytes in vitro: micronucleus induction. Evaluation of clastogenic and aneugenic potential using CREST and FISH assays.

Vlastos D, Stephanou G.

Department of Biology, University of Patras, Greece.

Cetirizine dihydrocloride, a widely administered antiallergic drug with the amine piperazine in its molecule, was studied as to its ability to cause micronucleus formation in human lymphocyte cultures treated in vitro. Peripheral lymphocytes from four different donors were cultured and treated with different concentrations of the compound. Cetirizine dihydrocloride was shown to induce enhanced micronucleus frequency in a dose-dependent manner, although lymphocytes from the different donors showed different susceptibilities to the compound. The content of induced micronuclei was investigated in one of the four donors by two independent assays, CREST (the application of antikinetochore antibodies) and FISH (fluorescence in situ hybridization) on cytochalasin B-formed binucleated cells. It was shown that the induced micronuclei resulted from breakage events as well as chromosome loss, thus characterizing cetirizine dihydrocloride as both clastogen and aneugen. Since our results were derived only from in vitro experiments, we believe that an extensive in vivo study is necessary before drawing conclusions as to the effects of cetirizine dihydrochloride in patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9705162&dopt=Abstract cetirizine Zyrtec



Zyrtec
A pharmacokinetic-pharmacodynamic modelling of the antihistaminic (H1) effects of cetirizine.

Urien S, Tillement JP, Ganem B, Kuch MD.

Laboratoire de Pharmacologie, Faculte de Medecine, Universite Paris XII, Creteil, France.

AIM: The pharmacokinetic-pharmacodynamic modelling developed here characterizes the time course of cetirizine effect on histamine-induced skin reactions (wheal and flare). METHOD: The model incorporated data from the study of Simons et al. [1993] in which the cetirizine plasma concentrations and the wheal and flare areas were recorded in a group of 6 patients after a 10 mg oral administration. RESULTS: The peak plasma concentration (>500 ng/ml) was rapidly reached in 1 h and the maximal effects were observed later at approximately 6 h. The cetirizine effect was ascribed to a physiologic indirect response model in which the drug concentration in the central compartment is linked to a response function that describes the inhibition or stimulation of the factors affected, input or output of response control. Cetirizine was characterized by two-compartmental kinetics with a rapid absorption phase (Ka = 1.0-1.4 h(-1)), a rapid distribution phase (alpha = 0.33-0.69 h(-1)) and a slower terminal half-life, 13.2-13.6 h (beta = 0.051-0.052 h(-1)). The total clearance was 1.4-1.5 l/h. Cetirizine effects on flare and wheal were characterized by the inhibition of the input factor (k(in)), the concentrations producing 50% of maximal effect (EC50) were 13 and 40 ng/ml and k(in) were 0.99 and 0.96 h(-1), respectively. These results were then used to simulate repeated daily oral administration of 10 mg cetirizine. CONCLUSION: At this dosage the histamine-induced flare was at least 80% inhibited at the start of the second administration Thereafter, on successive administrations, the inhibition was even more pronounced and the response control was nearly total.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10543317&dopt=Abstract cetirizine Zyrtec



Zyrtec
Treatment of perennial allergic rhinitis with cetirizine.

Amat P, Novella A, Roma J, Valero A, Lluch M, Malet A.

Al-Lergo Centre, Barcelona, Spain.

A study was made of 30 patients with perennial extrinsic rhinitis sensitized only to dust mites who were treated with cetirizine for 15 days, at a dose of 10 mg/24 hours. The following parameters were evaluated in each patient on day -1 before initiating treatment and on day 15: histamine 1/100 prick-test, Dermatohophagoides pteronyssinus prick-test, physical examination, assessment of nasal edema and rhinorrhea by anterior rhinoscopy, and of the degree of nasal obstruction by active anterior rhinomanometry. Each patient was given a form for daily clinical self-evaluation of the following subjective symptoms: sneezing, rhinorrhea, nasal obstruction, and nasal itchiness. The occurrence of side effects was evaluated. Cetirizine reduced significantly the area of the histamine and D. pteronyssinus papules elicited by prick-test. Clinical symptoms decreased significantly, with sneezing, nasal itchiness and rhinorrhea being greatly relieved, and nasal obstruction, evaluated by means of active anterior rhinomanometry performed before and after 15 days of treatment, being less alleviated. There was scant incidence of side effects in patients treated with cetirizine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1283054&dopt=Abstract cetirizine Zyrtec



Zyrtec
[Effect of cetirizine, selective H1 antagonist of histamine on skin and bronchial reactivity and cellular histamine release in allergic diseases]

[Article in Polish]

Siergiejko Z, Michalska I, Rogalewska A, Chyrek-Borowska S.

Kliniki Alergologii AM, Bialymstoku.

The study aimed at evaluating an effect of cetirizine--selective antagonist of histamine H1 receptor--on skin and bronchial reaction to histamine, and histamine release from the cells by pollen antigen and anti-IgE. Skin reactivity was tested thrice in 33 patients treated with Zyrtec (Polfa) for the chronic urticaria or allergic rhinitis. Reaction of the bronchi to histamine was tested with a technique described by Ryan et al in 10 asthmatic patients. As effect of cetirizine on histamine release from neutrophils was evaluated in patients with pollinosis before and on the fourth day of therapy. It was shown that the treatment with Zyrtec markedly decreases skin reaction to histamine. Single dose of drug administered 4 hours before the tests markedly restricts reactivity of the bronchi. Daily dose of 10 mg administered to patients with pollinosis stabilizes membranes of neutrophils.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1303774&dopt=Abstract cetirizine Zyrtec



Zyrtec
Cetirizine does not influence the immune response.

Canonica GW, Pesce G, Ruffoni S, Buscaglia S, Boero F, Jing G, Rihoux JP, Ciprandi G.

Allergy and Clinical Immunology Service, Department of Internal Medicine Genoa, Italy.

Antihistamines are frequently employed in the treatment of allergic rhinitis and urticaria-angioedema syndrome. We analyzed the in vitro effects of cetirizine on the immune response. To this end the proliferation of peripheral mononuclear cells induced by mitogen and by -CD3, -CD2, or -CD28 monoclonal antibodies has been studied. Since the plasma peak of cetirizine following ingestion of 10 mg is about 1 microgram/mL, the drug was tested in the cultures at the concentration of 0.1, 1, or 10 micrograms/mL. No influence of cetirizine on T cell proliferation was detected. We also evaluated the effect of cetirizine on the expression of the following markers expressed by T cells upon activation: lymphocyte markers ICAM-1, HLA-DR, and CD25 surface expression, alpha-1-acid glycoprotein has been also studied. There was no effect of cetirizine on the investigated immunologic parameters; these data acquire clinical relevance when related to previous reports showing a depression of the immunologic response exerted by other compounds such as ketotifen and theophylline and when related to the recent data about the modulation of ICAM-1 expression on eosinophils by cetirizine. Cetirizine does not affect ICAM-1 expression of lymphocyte membrane.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1347675&dopt=Abstract cetirizine Zyrtec



Zyrtec
Interference of cetirizine with the late eosinophil accumulation induced by either PAF or compound 48/80.

Martins MA, Pasquale CP, e Silva PM, Pires AL, Ruffie C, Rihoux JP, Cordeiro RS, Vargaftig BB.

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

1. The effect of topical or systemic treatment with the histamine H1-receptor antagonist, cetirizine, on the rat pleural eosinophil accumulation induced by PAF or compound 48/80 was investigated. The number of pleural resident eosinophils increased 6 h after the intrathoracic (i.t.) injection of PAF (1 microgram/cavity), peaked within 24 h and persisted significantly augmented for at least 96 h. Compound 48/80 (25 micrograms/cavity) also produced a long lasting pleural eosinophilia but this was first noted only 24 h after stimulation. 2. Intraperitoneal pretreatment with cetirizine inhibited eosinophilia induced by either PAF (ED50 = 19 mg kg-1) or compound 48/80 (ED50 = 14 mg kg-1) whereas meclizine, another histamine H1-receptor antagonist, was inactive. 3. Administered locally, cetirizine (5 and 15 micrograms/cavity) also dose-dependently inhibited both PAF- and compound 48/80-induced eosinophilia, providing evidence that its inhibitory effect is not due to any action upon circulating eosinophils. Consistent with this result, incubation of isolated peritoneal eosinophils with cetirizine failed to modify in vitro eosinophil migration caused by PAF. 4. Since the late eosinophilia induced by PAF may depend on the synthesis of a transferable protein mediator, cetirizine was administered to donor or recipient rats in order to determine whether it interferes with the generation or with the expression of this protein. We showed that only the treatment of recipient rats abolished the transfer of the eosinophilotactic activity, indicating that cetirizine does not modify the generation but inhibits the expression of this activity. 5. Our findings indicate that cetirizine is able to inhibit eosinophil accumulation by acting locally.(ABSTRACT TRUNCATED AT 250 WORDS)

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1350745&dopt=Abstract cetirizine Zyrtec