Zyrtec
Histamine H1 receptor antagonism by cetirizine in isolated guinea pig tissues: influence of receptor reserve and dissociation kinetics.

Christophe B, Carlier B, Gillard M, Chatelain P, Peck M, Massingham R.

UCB Pharma, Allergo-Respiratory Pharmacology Department, Chemin du Foriest, Batiment R1, B-1420 Braine l'Alleud, Belgium. Bernard.Christophe UCB-Group.com

We characterised histamine H(1) receptor antagonism by cetirizine and its enantiomers on isolated guinea pig ileum and trachea. Competitive or mixed (competitive and apparent noncompetitive) antagonism profiles were observed. The order of potency was: chlorpheniramine> or =mepyramine>levocetirizine>cetirizine> or =terfenadine>loratadine>dextrocetirizine. The inhibitory effects of cetirizine, levocetirizine, terfenadine and loratadine were slowly reversible compared to those of dextrocetirizine or mepyramine. Cetirizine and its enantiomers were inactive on L-type Ca(2+) channels. Reduction of the histamine H(1) receptor reserve by dibenamine in the ileum (100-fold higher than in the trachea) showed a gradual change from the competitive profile of dextrocetirizine and mepyramine to a mixed profile. The present results show that cetirizine and levocetirizine are selective competitive but slowly reversible histamine H(1) receptor antagonists. Their mixed antagonism profile observed in the trachea can be explained by the small receptor reserve present in this tissue compared to the ileum and their very slow dissociation rate from the histamine H(1) receptor.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12787835&dopt=Abstract cetirizine Zyrtec



Zyrtec
Long-term cetirizine treatment may reduce new sensitisations in allergic children: a pilot study.

Ciprandi G, Frati F, Marcucci F, Sensi L, Milanese M, Tosca MA.

Allergy-ENT Unit, Head Neck Dpt., San Martino Hospital, Genoa, Italy.

Experimental data demonstrate that mite allergy is characterized by persistent chronic inflammation. This suggests that long-term continuous treatment may be included in the global strategy of allergy management as recently reported. Moreover, most of allergic subjects show polysensitisation. We conducted a study to investigate whether a long-term cetirizine treatment may reduce the occurence of new sensitisations in children with mite allergy. This study was initially double-blind, randomized, and placebo-controlled, with two parallel groups of 10 children with mite allergy receiving either cetirizine or placebo daily. All children could assume cetirizine as rescue medication (i.e. symptomatic treatment). After six months, parents of continuously-treated children decided to continue the treatment for 3 years. Other subjects continued to assume cetirizine on symptomatic basis. All children were prospectively followed for other 3 years. Outcome measure was skin prick test, yearly performed. Cetirizine-continuously-treated group showed a significant lower incidence of new sensitisations (p = 0.002). In conclusion, cetirizine administered daily for prolonged periods (i.e. 3 years) may decrease the development of new sensitisations in monosensitised children, showing a potential effect of tertiary prevention of allergy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12872679&dopt=Abstract cetirizine Zyrtec



Zyrtec
P-glycoprotein influences the brain concentrations of cetirizine (Zyrtec), a second-generation non-sedating antihistamine.

Polli JW, Baughman TM, Humphreys JE, Jordan KH, Mote AL, Salisbury JA, Tippin TK, Serabjit-Singh CJ.

Preclinical Drug Metabolism and Pharmacokinetics, GlaxoSmithKline, Inc., P.O. Box 13398, Room: MAI.2213.2G, Research Triangle Park, North Carolina 27709, USA. joseph.w.polli gsk.com

Recent in vitro studies have suggested that P-glycoprotein (Pgp) and passive membrane permeability may influence the brain concentrations of non-sedating (second-generation) antihistamines. The purpose of this study was to determine the importance of Pgp-mediated efflux on the in vivo brain distribution of the non-sedating antihistamine cetirizine (Zyrtec), and the structurally related sedating (first-generation) antihistamine hydroxyzine (Atarax). In vitro MDR1-MDCKII monolayer efflux assays demonstrated that cetirizine was a Pgp substrate (B-->A/A-->B + GF120918 ratio = 5.47) with low/moderate passive permeability (PappB-->A = 56.5 nm/s). In vivo, the cetirizine brain-to-free plasma concentration ratios (0.367 to 4.30) were 2.3- to 8.7-fold higher in Pgp-deficient mice compared with wild-type mice. In contrast, hydroxyzine was not a Pgp substrate in vitro (B-->A/A-->B ratio = 0.86), had high passive permeability (PappB-->A + GF120918 = 296 nm/s), and had brain-to-free plasma concentration ratios >73 in both Pgp-deficient and wild-type mice. These studies demonstrate that Pgp-mediated efflux and passive permeability contribute to the low cetirizine brain concentrations in mice and that these properties account for the differences in the sedation side-effect profiles of cetirizine and hydroxyzine. Copyright 2003 Wiley-Liss, Inc. and the American Pharmacists Association

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14502547&dopt=Abstract cetirizine Zyrtec



Zyrtec
Cetirizine, an H1-receptor antagonist, suppresses the expression of macrophage migration inhibitory factor: its potential anti-inflammatory action.

Shimizu T, Nishihira J, Watanabe H, Abe R, Ishibashi T, Shimizu H.

Departments of Dermatology Molecular Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

BACKGROUND: H1-receptor antagonists are often effective in the treatment of allergic disorders such as atopic dermatitis. Cetirizine, a putative H1-receptor antagonist, has recently been shown to have anti-inflammatory properties through the inhibition of leucocyte recruitment and activation, and by the reduction of ICAM-1 expression on keratinocytes. OBJECTIVE: To further elucidate the anti-inflammatory properties of cetirizine, we first examined its effects on antigen-induced eosinophilia and neutrophila in vivo. We then examined the anti-inflammatory effects of cetirizine on a human keratinocyte A431cell line. METHODS: Mice were sensitized subcutaneously with ragweed pollen and were challenged intraperitoneally with the allergen. Cetirizine diluted in sterile water (0-20 mg/kg) or only sterile water was administered orally. Peritoneal cells were obtained at 8 and 24 h after challenge. The eosinophilia and neutrophilia induced by ragweed pollen extract were quantitated. Macrophage migration inhibitory factor (MIF), macrophage inflammatory protein 2 (MIP-2) and eotaxin contents of peritoneal fluid were also measured by mouse ELISA. The effects of cetirizine on MIF-induced IL-8 production in A431 cells were examined by ELISA. The effects of cetirizine on MIF expression and production in A431 cells were examined by human MIF ELISA and Northern blot analysis. RESULTS: Eosinophilia and neutrophilia induced by ragweed pollen extract were found to be significantly reduced in cetirizine-treated mice (20 mg/kg). MIF, a pleuripotent cytokine, was significantly decreased at 8 and 24 h in the peritoneal fluid by cetirizine treatment. MIP-2 and eotaxin were also decreased 8 and 24 h, respectively, after challenge in the peritoneal fluid with cetirizine treatment. MIF stimulates IL-8 production in A431 cells. We found that MIF production in A431 cells was inhibited by 10 microm cetirizine. Consistent with this, cetirizine significantly inhibited MIF-induced IL-8 production. CONCLUSION: These results suggest that cetirizine exerts its anti-inflammatory effects by inhibiting MIF as well as IL-8 production, such as those involved in inflammatory allergic skin disease, suggesting a broad spectrum of action beyond its mere H1-receptor-antagonistic function.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14720269&dopt=Abstract cetirizine Zyrtec



Zyrtec
[NMR studies on cetirizine hydrochloride]

[Article in Chinese]

Li Q, Shen WB, Zou QG.

Center for Instrumental Analysis, China Pharmaceutical University, Nanjing 210009, China.

AIM: To study the NMR phenomena of cetirizine hydrochloride and assign all proton and carbon signals in NMR spectra. METHODS: To record the 1D and 2D NMR spectra of cetirizine hydrochloride while changing the experimental temperature and adding D2O into the solution. RESULTS: More than one NMR signal or broad peak resulting from piperazine and the attached groups with N atom were given in DMSO-d6 solution at room temperature. "Coalescence" or narrowing had occurred for the proton and carbon signals when the experimental temperature was increased or D2O was added into the solution. CONCLUSION: Compared with the NMR "time scale", there are more than one conformation of cetirizine hydrochloride in DMSO-d6 solution at room temperature. The different conformation will be exchanged fast while temperature rise and the stable conformation will be existed while D2O was added into the solution.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14730901&dopt=Abstract cetirizine Zyrtec



Zyrtec
Oculogyric crisis in patients taking cetirizine.

Fraunfelder FW, Fraunfelder FT.

Casey Eye Institute, Oregon Health and Science University, Portland, Oregon 97201, USA. eyedrug ohsu.edu

PURPOSE: To report oculogyric crisis in patients receiving cetirizine and inform clinicians on the characteristics of this drug-induced ocular side effect. METHODS: For this retrospective, observational case series, case reports were collected from the National Registry of Drug-Induced Ocular Side Effects (Casey Eye Institute, Portland, Oregon). The World Health Organization Causality Assessment Guide of Suspected Adverse Reactions was used to categorize the cases. RESULTS: Nine cases were reported, with eight occurring in the pediatric age group. Dosage ranged from 5 to 10 mg orally and onset of symptoms ranged from 3 to 184 days. Six cases of oculogyric crisis had positive rechallenge data. Eight cases had complete neurologic consultation including radiographic studies. CONCLUSIONS: Cetirizine can cause oculogyric crisis, especially in the pediatric age group. Extensive neurologic workups may be avoided if clinicians recognize this drug-induced ocular side effect.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14962433&dopt=Abstract cetirizine Zyrtec