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Data were collected from two placebo-controlled trials and from official French databases. The effectiveness of the treatment was assessed by the mean number of pruritus-free days experienced by the patient within a 30-day period (PFD30). Direct cost parameters were medications used, medical procedures and hospitalisations for urticaria or treatment of adverse events. Productivity cost parameters were the workdays lost, defined as absenteeism and/or presenteeism, resulting from urticaria. The costing was performed using a French societal perspective. Costs were reported in euro (2002 values) and were standardised to a 30-day month. Whenever possible, incremental cost-effectiveness ratios (ICERs) were derived from these data.
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Second-generation, relatively nonsedating histamine H1-receptor antagonists (H1-RA) are extensively used worldwide for the symptomatic treatment of allergic rhinoconjunctivitis and chronic urticaria. Information about the pharmacokinetics and pharmacodynamics of these medications, while still incomplete, is now sufficient to permit optimisation of therapy. Published pharmacokinetic and pharmacodynamic information on these H1-RA is summarised here, and areas where more data are required are delineated. Serum concentrations of most second-generation H1-RA are relatively low, and are usually measured by radioimmunoassay. After oral administration, peak concentrations are observed within 2 or 3 h. Bioavailability has not been well studied, due to the lack of intravenous formulations. Most H1-RA are metabolised in the hepatic cytochrome P450 system: terfenadine, astemizole, loratadine, azelastine, and ebastine have 1 or more active metabolites which are present in serum in higher concentrations than the respective parent compound, and therefore can be measured by high performance liquid chromatography. Cetirizine, an active metabolite of the first generation H1-receptor antagonist hydroxyzine, is not further metabolised to any great extent in vivo, and is eliminated via renal excretion. Levocabastine is also eliminated primarily by excretion. Serum elimination half-life values differ greatly from 1 H1-RA to another, and are 24 h or less for terfenadine, astemizole, loratadine, cetirizine, azelastine and ebastine, and the active metabolites of terfenadine, loratadine and ebastine. The active metabolite of azelastine (demethylazelastine) has a serum elimination half-life value of about 2 days, while that of astemizole (demethyl-astemizole) has a value of 9.5 days. From the few published studies in which the apparent volumes of distribution of the second-generation H1-RA have been calculated, it appears that tissue distribution is extensive. In children, the half-lives of H1-RA are generally shorter than are found in adults; there is no published information on the pharmacokinetics of astemizole, loratadine, azelastine, or ebastine in children. In some elderly adults, terfenadine, loratadine and cetirizine may have longer half-lives than in young healthy adults. There is little published data on the pharmacokinetics of the second-generation H1-RA in patients with impaired hepatic function. The half-life of cetirizine is prolonged in those with impaired renal function. There is a paucity of information on the pharmacokinetics of H1-RA in neonates, in pregnancy or during lactation.(ABSTRACT TRUNCATED AT 400 WORDS)
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Histamine released from dermal mast cells plays a central role in the increased vascular permeability in acute urticaria, and administration of anti-histamines usually suppresses development of wheals. Acute idiopathic urticaria, particularly a severe case, occasionally presents with acute inflammatory reactions such as low-grade fever and leukocytosis and is resistant to anti-histamines. Considering the wide spectrum of proinflammatory cytokines and chemokines that can be released from activated mast cells, some of them might be involved in the pathogenesis of urticaria. We measured plasma levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-alpha) in 16 cases of severe acute urticaria. None of them showed elevated plasma levels of IL-8 or TNF-alpha. Nine out of 16 acute urticaria patients showed elevated circulating IL-6 with concomitant increases in serum CRP levels. All such patients were resistant to conventional anti-histamine treatment and required systemic steroids for complete suppression of wheal development. After subsidence of the urticaria, their elevated IL-6 and CRP levels dropped to their normal ranges. In contrast, all but one patient without elevated circulating IL-6 was successfully treated with a H1 receptor antagonist, cetirizine. The data suggest involvement of IL-6 in the pathogenesis of severe acute urticaria that is resistant to anti-histamines.
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Six patients with AD were challenged with Dermatophagoides pteronyssimus (DPT patch tests applied to clinically normal skin) and six patients with ACD challenged in the same way with allergens of the European standard series. Skin biopsies at challenged sites were performed before and 6, 24 and 48 h after challenge. The experiment was carried out under double-blind cross-over conditions during a 4-day treatment with a placebo and cetirizine.
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Antihistamines are widely used to treat allergy symptoms. First-generation antihistamines have adverse effects on the central nervous system (CNS), such as hypnotic and amnesic effects, whereas second-generation antihistamines have poor brain penetration, and therefore, have fewer CNS-related adverse effects. Memory consists of several phases, including acquisition, consolidation, expression, and extinction. It remains unclear whether these phases are affected by antihistamines. We investigated the effects of diphenhydramine, a first-generation antihistamine, and levocetirizine and olopatadine, second-generation antihistamines, on memory phases. Mice were subjected to fear conditioning on day 1 and tested on day 2. Antihistamines were administered before conditioning, immediately after conditioning, or before the test session. Diphenhydramine (30mg/kg) decreased freezing time when administered immediately after conditioning or before the test session. These effects were not attributable to a change in locomotor activity. Levocetirizine (0.1, 1, 10mg/kg) and olopatadine (1, 10, 20mg/kg) had no effects on conditioned fear. We also examined the effect of diphenhydramine and levocetirizine on the expression of an activity-dependent gene associated with the test session. Diphenhydramine, but not levocetirizine, increased Arc transcription in the central nucleus of the amygdala. These data indicate that diphenhydramine, but not levocetirizine or olopatadine, impairs the consolidation and expression of conditioned fear.
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Rupatadine is a once-daily, non-sedating, selective and long-acting new drug with a strong antagonist activity towards both histamine H(1) receptors and platelet-activating factor receptors. The use of rupatadine is indicated in adult and adolescent patients (> 12 years of age) suffering from intermittent and persistent allergic rhinitis and chronic idiopathic urticaria. In the treatment of these diseases, rupatadine is at least as effective as ebastine, cetirizine, loratadine and desloratadine. A very good safety profile of rupatadine has been evidenced in various studies, including a long-term (1-year) safety study. Rupatadine does not present drug-drug interactions with azithromycin, fluoxetine and lorazepam, but should not be administered concomitantly with known CYP3A4 inhibitors.
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An in vitro flow cytometric model has been developed to evaluate the effects of antiallergic drugs such as cetirizine (CTZ) on the expression of surface molecules on primary cultured normal cells. Quantitative analysis demonstrated that HLA class I and ICAM-1/CD54 molecules are present on both epithelial and stromal cells, and that their expression is strongly enhanced by treatment with interferon-gamma (IFN-gamma). Nevertheless, the IFN-gamma-mediated upregulation of ICAM-1/CD54 was inhibited by treatment with CTZ, demonstrating a direct effect on both cell types. This finding is particularly interesting because ICAM-1/CD54 is the main rhinovirus receptor, and rhinoviruses are the principal cause of asthma exacerbation in children. Thus, according to data derived from this in vitro model, CTZ should have an important role in the reduction of infectious exacerbation of asthma in atopic patients.
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A total of 47 children of both sexes aged between 2 to 6 years with allergy rhinitis (AR) were included in this study, who were randomly selected to be treated with Zyrtec (Cetirizine 2 HCL) drops 5 mg daily for 3 weeks. Investigators made a global evaluation with symptom scores before treatment and once a week for 3 weeks after treatment.
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Factors other than histamine are probably involved in the flare following APST in CU; such factors might play a pathogenic role particularly in patients not responding to standard antihistamine treatments.
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We report on an adolescent 18-year-old woman who developed delusional thinking and depression after starting treatment with cetirizine. Once cetirizine was discontinued, the patient returned to her clinical baseline.
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We evaluated the effects of second-generation antihistamines on the QoL of subjects with CIU using desloratadine as a treatment model. Desloratadine was selected because it is the most frequently assessed non-sedating second-generation antihistamine in QoL studies in patients with CIU.
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Original articles, reviews and consensus documents published from 1998 to 2006 and indexed in the MEDLINE and PubMed databases. Keyword: antihistamines.
To investigate the potential rules and knowledge of Traditional Chinese Medicine (TCM) and Western Medicine (WM) treatment on chronic urticaria (CU) based on data-mining methods.
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Cysteinyl-leukotrienes (CysLTs) are endogenous mediators of inflammation and play an important role in allergic airway disease by stimulating bronchoconstriction, mucus production, mucosal oedema and inflammation, airway infiltration by eosinophils, and dendritic cell maturation that prepares for future allergic response. Montelukast inhibits these actions by blocking type 1 CysLT receptors found on immunocytes, smooth muscle and endothelium in the respiratory mucosa. Initially developed as a treatment for asthma, montelukast has more recently found use in the treatment of allergic rhinitis (AR). We conducted a systematic review of studies that have evaluated montelukast in the treatment of seasonal AR (SAR) and perennial AR (PAR), with and without concomitant asthma. Primary consideration was given to large, randomised, placebo-controlled, double-blind clinical trials in which AR endpoints were assessed and the use of concurrent treatments for AR was excluded. Eight such studies were found in the literature. The primary endpoint in these was daytime nasal symptom severity represented by a composite score derived from individual self-ratings of nasal congestion, rhinorrhoea, nasal pruritus and sneezing. Secondary endpoints have included these individual nasal symptom scores, additional scores for eye, ear and throat symptoms, the impact of rhinitis on quality of sleep, global evaluations of outcome by patients and physicians, and measures of the severity of concomitant asthma. A general outcome was that patients treated with montelukast had significantly greater improvements in their symptoms of SAR and PAR than did patients who were given a placebo. As monotherapy, montelukast exhibited efficacy similar to that of loratadine, but less than that of the intranasally administered corticosteroid fluticasone propionate. The use of montelukast in combination with antihistamines such as loratadine or cetirizine has generally resulted in greater efficacy than when these agents were used alone, and in some studies has produced results comparable with intranasally applied corticosteroids. In patients with AR comorbid with asthma, montelukast treatment has resulted in significant improvements in both, compared with placebo. Montelukast is well tolerated and has a favourable safety profile; adverse events have occurred at similar frequencies in patients taking either montelukast or placebo. Montelukast provides an effective and well tolerated oral treatment for allergic airway inflammation in patients with SAR or PAR without asthma, and in patients in whom AR is comorbid with asthma.
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.
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University hospital medical information network (UMIN 000007483).
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The potential adverse central nervous system effects of H1-receptor antagonists have not been optimally studied in the elderly.
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Cetirizine hydrochloride has proved effective in reducing allergic symptoms and can inhibit the infiltration of eosinophils in allergic late-phase responses in the skin. Because eosinophils are likely to play an important role in allergic late-phase reactions, we studied the effect of cetirizine on early and late asthmatic reactions and on levels of eosinophil cationic protein (ECP) in the blood after allergen challenge.
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In a double-blind, placebo-controlled, single-dose, four-way crossover study, cetirizine 10 mg, hydroxyzine 50 mg, diphenhydramine 50 mg, or placebo were administered to 20 healthy subjects. Before and two to two and one-half hours after dosing, the latency of the P300 event-related potential (P300) at the central (Cz) and parietal (Pz) scalp electrodes, and the visual analogue scale for somnolence were recorded. Epicutaneous tests with histamine were performed, and serum H1-receptor antagonist concentrations were also measured.
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Acyclovir offered rapid resolution of clinical severity of PR from second week onwards without significantly increased adverse events as compared to supportive therapy alone.
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Our study demonstrates the advantages of cardiac myocytes over heterologously expressed hERG channels in predicting QT interval prolongation and TdP in man. The potencies of some drugs in cardiac myocytes were similar to hERG, but only myocytes were able to detect important changes in APD characteristics and display EADs predictive of arrhythmia development. We observed similar qualitative drug profiles in cardiac myocytes, dog Purkinje fibers, and animal and human telemetry studies. Therefore, isolated native cardiac myocytes are a better predictor of drug-induced QT prolongation and TdP than heterologously expressed hERG channels. Isolated cardiac myocytes, when used with high-throughput patch clamp instruments, may have an important role in screening potential cardiotoxic compounds in the early phase of drug discovery. This would significantly reduce the attrition rate of drugs entering preclinical and/or clinical development. The current kinetics and amplitudes of the cloned hERG channel were profoundly affected by temperature, significantly altering the potency of one drug (E-4031). This finding cautions against routine drug testing at room temperature compared to physiologic temperature when using the cloned hERG channel.
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To evaluate the effects of cetirizine hydrochloride (5 mg)-pseudoephedrine hydrochloride (120 mg) (cetirizine-D) twice daily on AR and asthma symptoms, pulmonary function, and asthma-related quality of life in 274 patients with confirmed seasonal AR and concomitant mild-to-moderate asthma.
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Eighty healthy volunteers were randomized for four double-blinded treatment with desloratadine 5 and 10 mg and levocetirizine 5 and 10 mg. Wheal and flare responses were produced by histamine. Measurements were performed just before the ingestion of antihistamines (baseline) and afterward at 30, 60, 240 min and 24 h. The values obtained for each antihistamine were compared with baseline values.
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To evaluate the effect and safety of acupuncture therapy on patients with moderate to severe allergic rhinitis.
Primary efficacy variable was the Total 5-Symptom Score (T5SS). Secondary variables included Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), Work Productivity and Activity Impairment-Allergy Specific (WPAI-AS) questionnaire, and Epworth Sleepiness Scale (ESS). Safety assessments were based on adverse events (AEs).