levocetirizine and desloratadine

Background Chronic spontaneous urticaria (CSU) is characterised by the development of crops of red, itchy, raised weals or hives with no identifiable external cause.Objectives To assess the effects of H1-antihistamines for CSU.Search methods We searched the following databases up to June 2014: Cochrane Skin Group Specialised Register, CENTRAL (2014, Issue 5), MEDLINE(from 1946), EMBASE (from 1974) and PsycINFO (from 1806). We searched five trials registers and checked articles for references to relevant randomised controlled trials.Selection criteria We included randomised controlled trials of H1-antihistamines for CSU. Interventions included single therapy or a combination of H1-antihistamines compared with no treatment (placebo) or another active pharmacological compound at any dose.Data collection and analysis We used standard methodological procedures as expected by The Cochrane Collaboration.Our primary outcome measures were proportion of participants with complete suppression of urticaria: 'good or excellent' response,50% or greater improvement in quality of life measures, and adverse events.We present risk ratios (RR) with 95% confidence intervals(CIs). Main results We identified 73 studies (9759 participants); 34 studies provided data for 23 comparisons. The duration of the intervention was up to two weeks (short-term) or longer than two weeks and up to three months (intermediate-term).Cetirizine 10mg once daily in the short term and in the intermediate term led to complete suppression of urticaria by more participants than was seen with placebo (RR 2.72, 95% CI 1.51 to 4.91). For this same outcome, comparison of desloratadine versus placebo in the intermediate term (5 mg) (RR 37.00, 95% CI 2.31 to 593.70) and in the short term (20 mg) (RR 15.97, 95% CI 1.04 to 245.04)favoured desloratadine, but no differences were seen between 5 mg and 10 mg for short-term treatment.Levocetirizine 20 mg per day (short-term) was more effective for complete suppression of urticaria compared with placebo (RR 20.87,95% CI 1.37 to 317.60), and at 5 mg was effective in the intermediate term (RR 52.88, 95% CI 3.31 to 843.81) but not in the shortterm, nor was 10 mg effective in the short term.Rupatadine at 10 mg and 20 mg in the intermediate term achieved a 'good or excellent response' compared with placebo (RR 1.35,95% CI 1.03 to 1.77).Loratadine (10 mg) versus placebo (RR 1.86, 95% CI 0.91 to 3.79) and loratadine (10 mg) versus cetirizine (10 mg) (RR 1.05, 95%CI 0.76 t

Topics: Cetirizine; Cyproheptadine; Histamine H1 Antagonists; Humans; Hydroxyzine; Loratadine; Randomized Controlled Trials as Topic; Urticaria

Bilastine is an orally administered, second-generation antihistamine used in the symptomatic treatment of seasonal or perennial allergic rhinoconjunctivitis and urticaria. In two well designed phase III trials, 14 days' treatment with bilastine was associated with a significantly lower area under the effect curve (AUEC) for the reflective total symptom score (TSS) than placebo in patients with symptomatic seasonal allergic rhinitis. Additionally, reflective nasal symptom scores were significantly lower in bilastine than placebo recipients in patients with a history of seasonal allergic rhinitis who were challenged with grass pollen allergen in a single-centre, phase II study. Neither bilastine nor cetirizine was effective in the treatment of perennial allergic rhinitis with regard to the mean AUEC for reflective TSS in another well designed phase III trial. However, results may have been altered by differences in some baseline characteristics and placebo responses between study countries. In another well designed phase III trial, compared with placebo, bilastine was associated with a significantly greater change from baseline to day 28 in the mean reflective daily urticaria symptom score in patients with chronic urticaria. There were no significant differences in primary endpoint results between bilastine and any of the active comparators used in these trials (i.e. cetirizine, levocetirizine and desloratadine). Bilastine was generally well tolerated, with a tolerability profile that was generally similar to that of the other second-generation antihistamines included in phase III clinical trials.

Topics: Area Under Curve; Benzimidazoles; Cetirizine; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Piperidines; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Perennial; Urticaria

Urticaria, and especially chronic spontaneous urticaria (CSU), is a difficult condition to treat. Consequently, clinicians need to use the best H(1)-antihistamines currently available and the pharmaceutical industries need to keep developing H(1)-antihistamines that are more effective than the ones we have today. To do this we need to be able to compare the clinical efficacy of both established and new drugs. Obviously, the ideal way to do this is to use head-to-head studies in CSU. However, such studies are extremely expensive and, in the case of novel molecules, have ethical and logistical problems. Consequently, we need to have predictive models. Although determination of Ki, an indicator of the in vitro potency of an H(1)-antihistamine, may help in the initial selection of candidate molecules, the large differences in volume of distribution and tissue accumulation in humans, precludes this from being a good predictor of clinical efficacy in CSU. From the data reviewed in this article, especially the direct comparative data of desloratadine and levocetirizine in weal and flare studies and CSU, weal and flare response would appear to be the best indicator we have of effectiveness of H(1)-antihistamines in clinical practice. However, it must be pointed out that the conclusion is, essentially, based on detailed comparisons of two drugs in studies sponsored by pharmaceutical companies. Consequently, to confirm the conclusions of this review, a multicentre study independent from the influence of pharmaceutical companies should be commissioned to compare the speed of onset and effectiveness of desloratadine, fexofenadine and levocetirizine in chronic spontaneous urticaria and against histamine-induced weal and flare responses in the same patients so that we have a clear understanding of the predictive value of our models.

Topics: Anti-Allergic Agents; Cetirizine; Histamine; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Predictive Value of Tests; Skin Tests; Terfenadine; Urticaria

Nasal congestion is the most troublesome symptom of allergic rhinitis (AR). First-generation and older second-generation antihistamines, while effective against nasal itching, sneezing, and rhinorrhea, have limited efficacy in relieving nasal congestion.. This review included nasal challenge studies and clinical trials that reported the effects on nasal congestion of the newer second-generation antihistamines desloratadine, fexofenadine, and levocetirizine.. MEDLINE and EMBASE were searched for nasal challenge studies and clinical trials published in English between January 1, 1991, and January 31, 2009, using the following terms, alone or in combination: antihistamines, second-generation antihistamines, allergic rhinitis, intermittent allergic rhinitis, perennial allergic rhinitis, persistent allergic rhinitis, seasonal allergic rhinitis, nasal challenge, nasal blockage, and nasal congestion. Studies that were not active or placebo controlled, that did not evaluate change in nasal congestion scores, or that focused on treatments other than desloratadine, fexofenadine, and levocetirizine for nasal congestion associated with AR were excluded.. Twenty-six clinical trials met the criteria for inclusion in the review. In 11 placebo-controlled trials that included objective assessment of nasal congestion, desloratadine, fexofenadine, and levocetirizine were associated with reductions in the severity of nasal congestion through maintenance of nasal airflow. The mean AUC for nasal airflow over 6 hours was significantly greater with desloratadine compared with placebo in 3 studies (P < 0.05); placebo-controlled trials of fexofenadine and levocetirizine had similar results. In 25 placebo- and active-controlled trials that reported subject-rated symptom scores, the 3 newer antihistamines were efficacious in the treatment of nasal congestion associated with AR. In 10 trials that reported objective and/or subjective measures, desloratadine was associated with significant improvements in nasal congestion compared with placebo (P < or = 0.05), beginning as early as the first 2 hours after allergen challenge. Fexofenadine was associated with significantly lower nasal congestion scores compared with placebo in 4 studies (P <- 0.05); nasal congestion scores were significantly reduced with levocetirizine in 3 placebo-controlled trials (P < or = 0.005).. In the studies reviewed, desloratadine, fexofenadine, and levocetirizine were effective in relieving the nasal congestion associated with AR compared with placebo. This effect began as early as day 2 and was consistent and progressive throughout treatment. Desloratadine, fexofenadine, and levocetirizine are appropriate options for the treatment of nasal congestion in patients with AR.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cetirizine; Child; Clinical Trials as Topic; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Male; Middle Aged; Nasal Obstruction; Rhinitis, Allergic, Seasonal; Terfenadine; Treatment Outcome; Young Adult

Second-generation histamine H(1) receptor antagonists were developed to provide efficacious treatment of allergic rhinitis (AR) and chronic idiopathic urticaria (CIU) while decreasing adverse effects associated with first-generation agents. When comparing the efficacy and safety profiles of the newest second-generation antihistamines - desloratadine, fexofenadine and levocetirizine - many pharmacological and clinical criteria must be considered. Most importantly, these elements should not be evaluated separately but, rather, as parts of a puzzle that create a whole picture. As a class, second-generation antihistamines are highly selective for the H(1) receptor. Some bind to it with high affinity, although there is marked heterogeneity among the various compounds. They have a limited effect on the CNS, and clinical studies have noted almost no significant drug-drug interactions in the agents studied. No major cytochrome P450 inhibition has been reported with desloratadine, fexofenadine and levocetirizine, and the bioavailability of desloratadine is minimally affected by drugs interfering with transporter molecules. Of the second-generation antihistamines, desloratadine has the greatest binding affinity for the H(1) receptor. The use of desloratadine, fexofenadine and levocetirizine is not associated with clinically relevant antimuscarinic effects. Desloratadine and fexofenadine do not impair cognitive or psychomotor functioning and are comparable with placebo in terms of somnolence. Based on these pharmacological characteristics, as well as clinical endpoints such as symptom scores, quality-of-life surveys, inflammatory cell counts and investigators' global evaluations, we conclude that desloratadine, fexofenadine and levocetirizine are all efficacious treatments for AR and CIU. However, differences among the antihistamines in relation to a lack of significant interaction with drug transporter molecules and somnolence in excess of placebo may provide some advantages for the overall profile of desloratadine compared with fexofenadine and levocetirizine.

Topics: Cetirizine; Drug Interactions; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Terfenadine; Urticaria

Topics: Cetirizine; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Piperazines; Retrospective Studies; Rhinitis, Allergic, Seasonal; Treatment Outcome

To perform a critical evaluation of the more recent H1 antihistamines and the various terms used to describe them, based on a review of evidence on their role in the treatment of allergic disorders.. Original articles, reviews and consensus documents published from 1998 to 2006 and indexed in the MEDLINE and PubMed databases. Keyword: antihistamines.. Second-generation antihistamines differ from first-generation ones because of their elevated specificity and affinity for peripheral H1 receptors and because of their lower penetration of the central nervous system (CNS), having fewer sedative effects as a result. Whilst second-generation antihistamines are in general better tolerated than their predecessors, some adverse effects, principally cardiotoxicity, have been observed with some of them. Over the last 20 years, new compounds with different pharmacokinetic properties have been synthesized. The majority of these exhibit anti-inflammatory properties that are independent of their action on the H1 receptor. More recent improvements, generally in the form of active metabolites, led to the use of the term third-generation antihistamines. This term emerged spontaneously, with no clear definition of its meaning or clinical implications, creating great confusion among healthcare professionals.. On the basis of the evidence on H1 antihistamines, none of them deserve the title "third-generation antihistamine." As the Consensus Group on New Generation Antihistamines concluded, to merit this definition, a new class of antihistamines would have to demonstrate distinct clinical advantages over existing compounds and fulfill at least three prerequisites: they should be free from cardiotoxicity, drug interactions and effects on the CNS.

Topics: Anti-Allergic Agents; Blood-Brain Barrier; Central Nervous System Diseases; Cetirizine; Child; Cyproheptadine; Heart Diseases; Histamine H1 Antagonists, Non-Sedating; Humans; Hypersensitivity; Loratadine; Mast Cells; Piperazines; Receptors, Histamine H1; Terfenadine

Allergic rhinitis (AR) is now recognised as a global health problem that affects 10-30% of adults and up to 40% of children. Each year, millions of patients seek treatment from their healthcare provider. However, the prevalence of AR maybe significantly underestimated because of misdiagnosis, under diagnosis and failure of patients to seek medical attention. In addition to the classical symptoms such as sneezing, nasal pruritus, congestion and rhinorrhoea, it is now recognised that AR has a significant impact on quality of life (QOL). This condition can lead to sleep disturbance as a result of nasal congestion, which leads to significant impairment in daily activities such as work and school. Traditionally, AR has been subdivided into seasonal AR (SAR) or perennial AR (PAR). SAR symptoms usually appear during a specific season in which aeroallergens are present in the outdoor air such as tree and grass pollen in the spring and summer and weed pollens in the autumn (fall); and PAR symptoms are present year-round and are triggered by dust mite, animal dander, indoor molds and cockroaches. Oral histamine H(1)-receptor antagonists (H(1) antihistamines) are one of the most commonly prescribed medications for the treatment of AR. There are several oral H(1) antihistamines available and it is important to know the pharmacology, such as administration interval, onset of action, metabolism and conditions that require administration adjustments. When prescribing oral H(1) antihistamines, the healthcare provider must take into account the clinical efficacy and weigh this against the risk of adverse effects from the agent. In addition to the clinical efficacy, potential for improvement in QOL with a particular treatment should also be considered.

Topics: Administration, Oral; Cardiovascular System; Central Nervous System; Cetirizine; Drug Interactions; Histamine H1 Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Long QT Syndrome; Loratadine; Piperazines; Practice Guidelines as Topic; Quality of Life; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Terfenadine; Treatment Outcome

Levocetirizine and desloratadine are newer antihistamines indicated for the treatment of allergic rhinitis and chronic idiopathic urticaria.. This article discusses the pharmacokinetics and pharmacodynamics of levocetirizine and desloratadine and reviews studies that have directly compared the effects of these 2 drugs in allergic rhinitis and urticaria.. Relevant articles were identified through a search of MEDLINE from 1999 through 2004 using the main search terms levocetirizine and desloratadine.. Levocetirizine is absorbed rapidly and reaches a steady-state plasma concentration more quickly than does desloratadine. It is also metabolized to a lesser extent than desloratadine, has a lower V(d), and has higher specificity for histamine(1) receptors. Eight well-controlled trials were identified that directly compared the effects of levocetirizine and desloratadine in the skin and nose of healthy individuals and patients with allergic rhinitis. Drug activity was measured in terms of wheal, flare, and itch reactions; nasal symptoms or symptom scores; increases in concentrations of inflammatory markers; or facial thermography. In most of these trials, levocetirizine had a faster onset and greater consistency of effect than desloratadine. The differences in the pharmacokinetic and pharmacodynamic profiles of the 2 drugs may partially explain these clinical findings.. Levocetirizine may be preferred to desloratadine as a treatment option for allergic rhinitis because of its faster onset of action and greater consistency of effect. Although comparative studies in chronic idiopathic urticaria are not available, data from histamine-induced wheal and flare studies in healthy volunteers suggest that levocetirizine may be more effective in preventing itching than desloratadine.

Topics: Cetirizine; Histamine Antagonists; Humans; Loratadine; Nose; Piperazines; Quality of Life; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Skin; Urticaria

Histamine is one of the most important steps in the phlogistic allergic reaction. Its activity is due to the link to specific receptors on the cellular surface. H1-receptors of second generation are the most currently prescribed drugs in allergic diseases for their high selectivity, little or no central sedative effect, rapid onset of action and long half lives. Antihistamines can modulate part of immunological mechanisms involved in the pathogenesis of allergic inflammation reducing mediator release and expression of adhesion molecules, regulating the release of cytokines, chemokines and consequently inflammatory cells recruitment. The anti-inflammatory effects of cetirizine, desloratadine and levocetirizine are reviewed. Quality of life is considered too, as a main parameter in a global evaluation of the antihistamine's effects.

Topics: Anti-Allergic Agents; Anti-Inflammatory Agents; Cetirizine; Histamine H1 Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Hypersensitivity; Loratadine; Piperazines; Quality of Life

Abstract Absorption, distribution, metabolism and excretion of desloratadine, fexofenadine, levocetirizine, and mizolastine in humans have been compared. The time required to reach peak plasma levels (tmax) is shortest for levocetirizine (0.9 h) and longest for desloratadine (> or =3 h). Steady-state plasma levels are attained after about 6 days for desloratadine, 3 days for fexofenadine, 2-3 days for mizolastine and by the second day for levocetirizine. The apparent volume of distribution is limited for levocetirizine (0.4 L/kg) and mizolastine (1-1.2 L/kg), larger for fexofenadine (5.4-5.8 L/kg) and particularly large for desloratadine (approximately 49 l/kg). Fexofenadine and levocetirizine appear to be very poorly metabolized (approximately 5 and 14% of the total oral dose, respectively). Desloratadine and mizolastine are extensively metabolized. After administration of 14C-levocetirizine to healthy volunteers, 85 and 13% of the radioactivity are recovered in urine and faeces, respectively. In contrast, faeces are the preferential route of excretion for 14C-fexofenadine (80% vs. 11% of the radioactive dose in urine). The corresponding values are 41% (urine) and 47% (faeces) for 14C-desloratadine, 84-95% (faeces) and 8-15% (urine) for 14C-mizolastine. The absolute bioavailability is 50-65% for mizolastine; it is high for levocetirizine as the percentage of the drug eliminated unchanged in the 48 h urine is 77% of the oral dose; the estimation for fexofenadine is at least 33%; no estimation was found for desloratadine. Fexofenadine is a P-glycoprotein (P-gp) substrate and P-gp is certainly involved both in the poor brain penetration by the compound and, at least partially, in a number of observed drug interactions. An interaction of desloratadine with P-gp has been suggested in mice, whereas the information on mizolastine is very poor. The fact that levocetirizine is a substrate of P-gp, although weak in an in vitro model, could contribute to prevent drug penetration into the brain, whereas it is unlikely to be of any clinical relevance for P-gp-mediated drug interactions.

Topics: Absorption; Animals; Area Under Curve; Benzimidazoles; Biological Availability; Cetirizine; Histamine H1 Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Metabolic Clearance Rate; Piperazines; Terfenadine; Tissue Distribution

Antihistamines are accepted in the therapy of allergic seasonal and perennial rhinitis. In the paper some anti-inflammatory effects of antihistamines have been presented, and their action mechanisms and clinical applications have been discussed in relation to the new preparates of antihistamines.

Topics: Cetirizine; Histamine H1 Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Hypersensitivity; Loratadine; Piperazines; Terfenadine

Topics: Acetates; Animals; Area Under Curve; Cetirizine; Half-Life; Histamine H1 Antagonists, Non-Sedating; Humans; Hypersensitivity; Loratadine; Piperazines; Randomized Controlled Trials as Topic

No comparative study of antihistamines that differ in structural system has been conducted in allergic rhinitis.. This was a randomized, double-blind, crossover comparative study to verify the efficacy of antihistamines that differ in structural system.. A total of 50 patients with moderate or more severe Japanese cedar pollen-induced allergic rhinitis were randomized to receive either placebo, desloratadine 5 mg (a tricyclic), or levocetirizine 5 mg (a piperazine). One dose of the study drug was orally administered at 9 pm on the day before a pollen exposure test, which was performed for 3 h (9 a.m. to 12 p.m.) to assess symptoms in an environmental challenge chamber (ECC). Nasal and ocular symptoms were compared at an airborne pollen level of 8,000 grains/m3. The primary endpoint was mean total nasal symptom score (TNSS) from 120 to 180 min in the ECC. Subjects with a difference of ≥1 in TNSS between 2 drugs were extracted to the relevant drug-responsive group.. The difference in TNSS from placebo was -2.42 (p < 0.0001) with levocetirizine and -1.66 (p < 0.01) with desloratadine, showing that both drugs were significantly more effective than placebo in controlling symptoms, but with no statistically significant difference between the 2 drugs. There were 12 subjects in the desloratadine-responsive group and 24 subjects in the levocetirizine-responsive group, with no contributor to response was detected.. Levocetirizine tended to control nasal symptoms more effectively than desloratadine. However, the response to each antihistamine varied among individuals and the predictors to the response are unknown.. UMIN ID: UMIN000029653.

Topics: Adult; Cedrus; Cetirizine; Cross-Over Studies; Double-Blind Method; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Male; Placebos; Pollen; Rhinitis, Allergic, Seasonal

Levocetirizine and desloratadine are mostly used as H1-antihistamines in the treatment of allergic disease in 5 and 10 mg doses.. In this study, the efficacy of single oral dosages of 5 and 10 mg desloratadine and levocetirizine were compared by using histamine-induced wheal and flare reactions.. 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.. It was found that except the flare reactions at 30th min, levocetirizine 5 and 10 mg suppressed histamine-induced wheal and flare reactions more than desloratadine 5 and 10 mg did. There were not any significant differences between desloratadine 5 and 10 mg in all periods. Levocetirizine 10 mg suppressed wheal and flare reactions significantly more than levocetirizine 5 mg only at 24th h.. In this study, it was observed that levocetirizine 5 and 10 mg had a higher activity than desloratadine 5 and 10 mg.

Topics: Administration, Oral; Adult; Anti-Allergic Agents; Cetirizine; Cross-Over Studies; Double-Blind Method; Female; Healthy Volunteers; Histamine; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Male; Middle Aged; Time Factors; Urticaria; Young Adult

H(1)-antihistamines are first line treatment of chronic urticaria, but many patients do not get satisfactory relief with recommended doses. European guidelines recommend increased antihistamine doses of up to 4-fold.. To provide supportive evidence for the European guidelines.. Eighty tertiary referral patients with chronic urticaria (age range, 19-67 years) were randomized for double-blind treatment with levocetirizine or desloratadine (40/40). Treatment started at the conventional daily dose of 5 mg and then increased weekly to 10 mg, 20 mg, or 20 mg of the opposite drug if relief of symptoms was incomplete. Wheal and pruritus scores, quality of life, patient discomfort, somnolence, and safety were assessed.. Thirteen patients became symptom-free at 5 mg (9 levocetirizine vs 4 desloratadine), compared with 28 subjects on the higher doses of 10 mg (8/7) and 20 mg (5/1). Of the 28 patients nonresponsive to 20 mg desloratadine, 7 became symptom-free with 20 mg levocetirizine. None of the 18 levocetirizine nonresponders benefited with 20 mg desloratadine. Increasing antihistamine doses improved quality of life but did not increase somnolence. Analysis of the effect of treatment on discomfort caused by urticaria showed great individual heterogeneity of antihistamine responsiveness: approximately 15% of patients were good responders, approximately 10% were nonresponders, and approximately 75% were responders to higher than conventional antihistamine doses. No serious or severe adverse effects warranting discontinuation of treatment occurred with either drug.. Increasing the dosage of levocetirizine and desloratadine up to 4-fold improves chronic urticaria symptoms without compromising safety in approximately three quarters of patients with difficult-to-treat chronic urticaria.

Topics: Adult; Aged; Cetirizine; Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Male; Middle Aged; Quality of Life; Urticaria; Young Adult

Topics: Cetirizine; Chronic Disease; Double-Blind Method; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Male; Pilot Projects; Sleep Stages; Urticaria

Nonsedating H(1)-antihistamines are recommended for the treatment of urticaria by the recent EAACI/GA(2)LEN/EDF guidelines. The aim of this study was to compare the efficacy, after 4 weeks of treatment, with levocetirizine 5 mg and desloratadine 5 mg, both once daily in the morning, in symptomatic chronic idiopathic urticaria (CIU) patients.. This multi-center, randomized, double-blind study involved 886 patients (438 on levocetirizine and 448 on desloratadine). The primary objective was to compare their efficacy on the mean pruritus severity score after 1 week of treatment. Mean pruritus severity score over 4 weeks and pruritus duration score, number and size of wheals, mean CIU composite score (sum of the scores for pruritus severity and numbers of wheals), quality of life, and the patient's and investigator's global satisfaction with treatment, were secondary efficacy measures.. Levocetirizine led to a significantly greater decrease in pruritus severity than desloratadine over the first treatment week; mean pruritus severity scores of 1.02 and 1.18 for levocetirizine and desloratadine, respectively (P < 0.001). The result was similar for the entire 4-week treatment period (P = 0.004). In addition, levocetirizine decreased pruritus duration and the mean CIU composite scores to a significantly greater extent than desloratadine during the first week (P = 0.002 and 0.005, respectively) and over the entire study (P = 0.009 and P < 0.05, respectively). Similarly, levocetirizine increased the patients' global satisfaction after one and 4 weeks (P = 0.012 and 0.021, respectively), compared with desloratadine. Safety and tolerability were similar in both groups.. Levocetirizine 5 mg was significantly more efficacious than desloratadine 5 mg in the treatment of CIU symptoms.

Topics: Cetirizine; Chronic Disease; Double-Blind Method; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Male; Pruritus; Quality of Life; Severity of Illness Index; Urticaria

Persistent allergic rhinitis often impairs quality of life.. We assessed the extent to which treating persistent allergic rhinitis with montelukast, desloratadine, and levocetirizine alone or in combination improved quality of life.. A 32-week randomized, double-blind, placebo-controlled, crossover study was performed in 2 arms: 20 patients received montelukast 10 mg/d and/or desloratadine 5 mg/d or placebo; 20 patients received montelukast 10 mg/d and/or levocetirizine 5 mg/d or placebo. The treatment periods were separated by 2-week washout periods. Quality of life was assessed on the day before starting treatment and on the last day of each treatment period using the Rhinoconjunctivitis Quality of Life Questionnaire. Sleep problems were also assessed.. In the desloratadine plus montelukast arm, the mean (SEM) quality of life score before treatment was 3.1 (0.41). After placebo, this score was 2.16 (0.43), after desloratadine it was 1.79 (0.38), after montelukast it was 1.48 (0.37), and after montelukast plus desloratadine it was 1.59 (0.37). In the montelukast plus levocetirizine arm, the mean quality of life score before treatment was 2.58 (0.49). After placebo it was 1.78 (0.46), after levocetirizine it was 1.38 (0.42), after montelukast it was 1.36 (0.37), and after montelukast plus levocetirizine it was 1.26 (0.39).. Placebo, montelukast, desloratadine and levocetirizine significantly improved quality of life. Combining montelukast with either levocetirizine or desloratadine gave additional benefits in comparison to each agent alone and could be considered for patients whose quality of life is impaired by persistent allergic rhinitis.

Topics: Acetates; Adolescent; Adult; Aged; Cetirizine; Chronic Disease; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Drug Interactions; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Leukotriene Antagonists; Loratadine; Male; Middle Aged; Quality of Life; Quinolines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Sulfides; Treatment Outcome

The reproducible and standardized histamine-induced wheal and flare model helps identify the objective effectiveness of antihistamines in humans, as well as their differences in onset and duration of action. Some of the newest antihistamines have already been compared in a head-to-head setting using this model. However, their objective action at inhibiting the allergen-induced wheal and flare response has not been reported yet.. The time-response study presented here shows the objective activity of two of the newest generation of antihistamines, levocetirizine and desloratadine, at inhibiting the allergen-induced wheal and flare response in a randomized, cross over, placebo-controlled trial. This model is interesting to the clinical setting since allergic subjects are recruited, and the response to allergen involves mast cell degranulation and release of numerous vasoactive and pro-inflammatory mediators additionally to histamine. In addition, this study reports receptor occupancy for both antihistamines at therapeutic dosage, leading to analysis of potential differences in activity. This study clearly shows the potential anti-inflammatory properties of desloratadine and levocetirizine in their skin activity when allergen is the challenging agent as occurs in the clinical situation.. To evaluate the inhibitory activity of the new-generation antihistamines levocetirizine and desloratadine at their therapeutic doses on the allergen-induced wheal and flare reaction at 1.5 h, 4 h, 7 h, 12 h and 24 h postdose, and to measure their plasma and skin concentrations.. A double-blind, randomized, cross-over, placebo-controlled study in 18 allergic subjects was carried out. The time-response of the wheal and flare reaction areas under the curve (AUC) were compared by anova.. Both antihistamines significantly (P < 0.001) inhibited the allergen-induced wheal and flare reactions compared with placebo. Levocetirizine was significantly more potent than desloratadine. Mean +/- SEM wheal AUC(0-24 h) was 506.4 +/- 81.0 with levocetirizine and 995.5 +/- 81.0 mm(2) h with desloratadine as compared with placebo (1318.5 +/- 361.0 mm(2) h). Flare AUC(0-24 h) was 5927.3 +/- 1686.5 and 15838.2 +/- 1686.5 mm(2) h, respectively [P < 0.001 for both compared with placebo (22508.2 +/- 7437.1 mm(2) h)]. Levocetirizine showed significant inhibition of wheal and flare already at 1.5 h postdose compared with placebo (P

Topics: Adolescent; Adult; Allergens; Cetirizine; Cholinergic Antagonists; Cross-Over Studies; Double-Blind Method; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Male; Middle Aged; Piperazines; Prospective Studies; Urticaria

The histamine-induced wheal and flare response was used to compare quantitatively the antihistaminic potency of levocetirizine and desloratadine.. In this double-blind, placebo-controlled crossover study, 24 healthy male non-atopic volunteers received weekly single doses of 1.25, 2.5 or 5 mg levocetirizine, 2.5, 5 or 10 mg desloratadine, or placebo. Four hours after dosing, histamine (100 mg/ml) skin prick tests were performed on the volar surface of both forearms. The diameters of the wheals and flares were measured 10 minutes later. Sedation was evaluated using a visual analogue scale and a motricity test. The effects of individual drug doses were compared using Student's t-test for paired data and the overall effects of the two drugs by ANOVA.. All doses of levocetirizine significantly (P < 0.0001) inhibited both wheals and flares in a dose-related manner. Only the 10 mg dose of desloratadine achieved significant inhibition of response. ANOVA showed levocetirizine to be significantly (P < 0.0001) more active than desloratadine. Neither drug caused significant sedation or loss of motricity.. Levocetirizine is significantly more effective than desloratadine in inhibiting wheal and flare responses to histamine in human skin in vivo, with 1.25 mg levocetirizine being more effective than 10 mg desloratadine.

Topics: Adult; Cetirizine; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Histamine; Histamine H1 Antagonists, Non-Sedating; Humans; Hypersensitivity, Immediate; Loratadine; Male; Middle Aged; Piperazines; Skin; Skin Tests; Urticaria

Desloratadine and levocetirizine are histamine H(1) receptor antagonists (antihistamines) that were launched in the UK in 2001. Our objective was to compare the frequency with which drowsiness and sedation were reported for desloratadine and levocetirizine within the first 30 days of observation, as monitored using the observational cohort technique of prescription-event monitoring (PEM).. Exposure data were derived from dispensed prescriptions written by primary care physicians and outcome data were derived from questionnaires that were posted to prescribers at least 6 months after the date of the first prescription for each patient. The odds ratio (OR) was calculated using unconditional logistic regression modelling. The effect of age, sex, reported prescribing indication (allergic rhinitis with asthma/wheezing, allergic rhinitis without asthma/wheezing, 'other'), pattern of use and reported previous antihistamine use on the OR was examined. A time-to-event analysis was performed.. The cohorts comprised >24,000 patients in total. Cohort demographics were similar (both cohorts: median age 37 years; 60% women); the most frequently reported prescribing indication for both drugs was allergic rhinitis without asthma/wheezing (54%). The incidence of first reports of drowsiness/sedation for levocetirizine or desloratadine was low (46 [0.37%] and 9 [0.08%], respectively) and statistically different (p < 0.0001). These events tended to occur earlier for desloratadine than levocetirizine (50% at 7 or 14 days of observation, respectively; p = 0.6487), but the cumulative time to event differed, with more events observed for levocetirizine than expected (p < 0.0001; 46 vs 28.09). The final estimates of risk were the sex-adjusted ORs for each prescribing indication category: allergic rhinitis with asthma/wheezing (3.51; 95% CI 0.71, 17.43; n = 3357), allergic rhinitis without asthma/wheezing (6.75; 95% CI 2.37, 19.22; n = 12,627) and 'other' (3.11; 95% CI 0.86, 11.31; n = 6725).. Although the reporting rates of drowsiness and sedation are low for both drugs, patients prescribed levocetirizine are more likely to experience drowsiness and sedation in the first month of observation (after starting treatment) than patients prescribed desloratadine. For patients with allergic rhinitis without asthma/wheezing, the sex-adjusted odds of drowsiness/sedation were over six times greater in patients using levocetirizine than desloratadine in the first month of observation, with the OR being statistically significant. For the other two indication categories, allergic rhinitis with asthma/wheezing and 'other', the OR was not statistically significant.. Although the risk of drowsiness/sedation is low, conditions such as allergic rhinitis are common, which makes any impact on patient cognitive function important. Doctors should be aware of this when prescribing these products to patients where daytime sedation is undesirable. However, essential components of the comparative benefit-risk evaluation of these two products include assessment of efficacy and patient preference (neither of which forms part of this study).

Topics: Adult; Cetirizine; Cohort Studies; Conscious Sedation; Drug Monitoring; England; Female; Histamine H1 Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Male; Middle Aged; Piperazines; Rhinitis; Sleep Stages

Montelukast sodium is approved as a treatment for intermittent and persistent allergic rhinitis (AR), but it has not been evaluated as combined therapy with antihistamines for persistent AR.. To investigate the effects of 6 weeks of treatment of persistent AR with desloratadine, levocetirizine, or montelukast alone or in combination.. A randomized, double-blind, placebo-controlled crossover study was performed. Patients were assigned to 2 arms: 20 received montelukast, 10 mg/d, desloratadine, 5 mg/d, or both or placebo and 20 received montelukast, levocetirizine, or both, 5 mg/d, or placebo. The treatment periods were separated by 2-week washout periods. Symptom scoring, skin prick tests, spirometry, rhinometry, and nasal lavage were performed the day before and the last days of the treatment periods. Eosinophil cationic protein levels were evaluated by means of nasal lavage.. The mean +/- SD total baseline nasal symptom score was 7.7 +/- 0.49 before treatment, 3.74 +/- 0.54 after desloratadine use, 3.6 +/- 0.48 after montelukast use, and 3.04 +/- 0.4 after montelukast-desloratadine use. The mean +/- SD baseline nasal symptom score was 7.95 +/- 0.68 before treatment, 3.02 +/- 0.64 after levocetirizine use, 3.44 +/- 0.55 after montelukast use, and 2.14 +/- 0.39 after montelukast-levocetirizine use. The greatest improvement in nasal symptoms occurred after combination treatment. Decreases in the level of eosinophil cationic protein were greater after the combined use of montelukast and antihistamine than after each agent given alone.. For persistent AR, the combination of montelukast and either desloratadine or levocetirizine is more effective than monotherapy with these agents.

Topics: Acetates; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Cetirizine; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Eosinophil Cationic Protein; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Male; Middle Aged; Nasal Lavage Fluid; Piperazines; Quinolines; Rhinitis, Allergic, Perennial; Rhinometry, Acoustic; Sulfides; Treatment Outcome

of this study was to compare the effect of the following antihistamines: cetirizine 10mg, desloratadine 5mg, fexofenadine 120 and 180mg, levocetirizine 5mg, loratadine 10mg, and placebo, administered in the recommended doses over the period of 5 days, on the visually assessed histamine-induced skin reaction, using the Laser Doppler flowmetry (LDF).. Forty two volunteers (aged 18-22) who gave a written consent before entering the study, were randomized in seven groups of six subjects each. The skin prick test with histamine solution of 10mg/ml was performed on the ventral forearm, 10 cm from the elbow, before and at 2, 4, 6, 8, 10, 12, 18, and 24 hours after drug administration, as well as once daily for the next 4 days of antihistamine drug or placebo intake, and 9 days following the treatment. Diameters of wheal and flare as well as the LDF index measured with Periflux PF3 flowmeter and skin probe, 5mm from the histamine-provoked area, were assessed 10 minutes after performing the above-mentioned skin prick test.. The current study revealed that during the 5-day treatment with recommended doses of cetirizine, desloratadine, fexofenadine, levocetirizine, and loratadine, a significant reduction of histamine-induced wheal, flare and the LDF index was observed as compared to the initial values and placebo intake, reaching the maximum value within the first 24 hours, weakening on the next day, and then gradually increasing during the following days. After the 5-day treatment drugs used for the study were lined up according to the volume of reduction in histamine-induced skin reaction (largest>smallest): levocetirizine > cetirizine > fexofenadine 180mg = fexofenadine 120mg > loratadine = desloratadine.. Following the end of the treatment, the effect of the antihistamines on skin reaction was subsiding in such an order: after 24 hours in case of loratadine and desloratadine, after two days for both doses of fexofenadine, and 3-4 days for cetirizine and levocetirizine.

Topics: Administration, Oral; Adult; Cetirizine; Double-Blind Method; Drug Administration Schedule; Histamine; Histamine H1 Antagonists, Non-Sedating; Humans; Laser-Doppler Flowmetry; Loratadine; Male; Piperazines; Regional Blood Flow; Skin; Skin Tests; Terfenadine; Treatment Outcome; Urticaria

The aim of the study was to compare the effect of inhibition skin reactivity after administration of single dose administration of various second generation antihistamines in the healthy people group.. Forty two healthy subjects (aged 22+/-18 years) were randomized into seven groups which received orally: cetirizine 10 mg, loratadine 10 mg, desloratadine 5 mg, levocetirizine 5 mg, fexofenadne 120 mg and 180 mg, or placebo respectively. The skin microcirculation reaction after 10 mg/ml histamine administration was estimated visually on the forearm (diameter of wheal and flare) and by Laser Doppler flowmetry before and after study drug or placebo administration prior and, 2, 4, 6, 8, 10, 12, 18, 24 h and one time daily every next 9 days.. There were significant differences of histamine-induced wheal, flare and skin blood flow inhibition vs baseline and placebo after drug administration. There were different dyr'mmics in suppression effect after histamine-induced skin reactivity in various drug groups. The overall inhibitory potency was statistically higher for cetirizine, levocetirizine and fexofenadine (even 95% ve basline) as compared to loratadine and desloratadine (even 65% vs basline). Different times of retreated inhibition effect after administered drugs were observed.. The study drugs shown significant different dynamics of skin reaction inhibition vs baseline and placebo. There were observed strongest effect after levocetirizine and cetirizine and next order after fexofenadine, desloratadine and loratadine.

Topics: Administration, Oral; Adult; Cetirizine; Double-Blind Method; Histamine; Histamine H1 Antagonists, Non-Sedating; Humans; Laser-Doppler Flowmetry; Loratadine; Male; Piperazines; Placebos; Skin; Skin Tests; Terfenadine; Treatment Outcome; Urticaria

Nasal obstruction is the main symptom in patients with perennial allergic rhinitis. Some new antihistamines have been demonstrated to be capable of improving this symptom.. The aim of this pilot study was to evaluate nasal symptoms, nasal airflow, eosinophils, and IL-4 in patients with perennial allergic rhinitis, before and after treatment with two new antihistamines: desloratadine and levocetirizine.. Thirty patients with perennial allergic rhinitis were evaluated, 26 males and 4 females (mean age 26+/-7.1 years). All of them received either desloratadine (5 mg/daily) or levocetirizine (5 mg/daily) or placebo for 4 weeks. The study was double-blind, parallel-group, placebo-controlled, and randomized. Total symptom score (including: rhinorrhea, nasal itching, sneezing, and nasal obstruction) was assessed before and after treatment. Rhinomanometry and decongestion test, nasal lavage, and nasal scraping were performed in all subjects before and after treatment. Eosinophils were counted by conventional staining; IL-4 was measured by immunoassay of fluids recovered from nasal lavage.. Desloratadine and levocetirizine treatment induced significant symptom relief and significant reduction of IL-4. Both antihistamines significantly affected all parameters in comparison with placebo.. This pilot study demonstrates the effectiveness of antihistaminic treatment in: i) relieving nasal symptoms, including obstruction, ii) improving nasal airflow, iii) exerting decongestant activity, iv) reducing eosinophil infiltration, and v) diminishing IL-4 levels.

Topics: Adolescent; Adult; Cetirizine; Double-Blind Method; Eosinophils; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Inflammation; Interleukin-4; Leukocyte Count; Loratadine; Male; Nasal Lavage Fluid; Nasal Mucosa; Nasal Obstruction; Pilot Projects; Piperazines; Rhinitis, Allergic, Perennial; Rhinomanometry

The Environmental Exposure Unit, an indoor pollen challenge system to test anti-allergic medications, was used to compare the onset and duration of action and the efficacy of levocetirizine and desloratadine, two recently developed H1-antagonists. In this double-blind, placebo-controlled, parallel-group study, qualified subjects were randomised to once-daily levocetirizine 5 mg (n = 141), desloratadine 5 mg (n = 140) or placebo (n = 92) and exposed to ragweed pollen on two consecutive days (7 h and 6 h). Symptoms were self-rated every 30 min. On both days, levocetirizine produced a greater improvement in the major symptom complex score (primary efficacy variable) than desloratadine (p = 0.015); both were better than placebo (p < 0.001). Levocetirizine acted earlier (1 h vs. 3 h) and produced greater symptom relief at 24 h than desloratadine (p = 0.003). Levocetirizine also alleviated nasal obstruction better than desloratadine (p = 0.007) on day 1; and better than placebo (p = 0.014) after the second dose on day 2, which was not observed with desloratadine. Levocetirizine and desloratadine were safe and well tolerated.

Topics: Adolescent; Adult; Cetirizine; Cohort Studies; Double-Blind Method; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Male; Piperazines; Rhinitis, Allergic, Seasonal; Severity of Illness Index; Treatment Outcome

Summary Background There are no data directly comparing the relative efficacy of modern H(1)-antihistamines in allergic rhinitis using nasal provocation challenge. Objective We elected to study the comparative effectiveness of usual clinically recommended doses of desloratadine (DES), fexofenadine (FEX), and levocetirizine (LEV), on nasal adenosine monophosphate (AMP) challenge in patients with perennial allergic rhinitis (PAR). Methods 16 patients with PAR were randomized in double-blind cross-over fashion to receive single doses of DES 5 mg, FEX 180 mg, LEV 5 mg, or placebo (PL), with nasal AMP challenge performed 12 h after dosing. Measurements of peak nasal inspiratory flow (PNIF) were made over 60 min after nasal AMP challenge. Results Pre-challenge values (mean+/-SEM) for PNIF (L/min) were not significantly different comparing all groups; DES (129+/-9), FEX (128+/-11), LEV (128+/-13), and PL (128+/-12). The maximum % PNIF fall from baseline over 60 min after nasal AMP challenge was significantly attenuated (P<0.05) compared to PL (50+/-4), with DES (32+/-5), FEX (36+/-4), and LEV (36+/-4). The area under the 60-min time-response curve (%.min) was also significantly attenuated (P<0.05) compared to PL (2110+/-268), with DES (1126+/-285), FEX (1225+/-255), and LEV (1261+/-194). There were no significant differences between the three H(1)-antihistamines for any outcomes. Conclusion DES, FEX, and LEV were equally effective in attenuating the response to nasal AMP challenge. However, further long-term studies will be required to study their comparative effects on nasal symptoms, quality of life, as well as on nasal inflammatory cells.

Topics: Adenosine Monophosphate; Adult; Aged; Aged, 80 and over; Anti-Allergic Agents; Cetirizine; Cross-Over Studies; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Loratadine; Male; Middle Aged; Nasal Provocation Tests; Piperazines; Rhinitis, Allergic, Perennial; Terfenadine; Treatment Outcome

Direct comparisons of antihistamines are rare but very much needed. Newly available antihistamine preparations, levocetirizine, the R-enantiomer of racemate cetirizine, and desloratadine, an active metabolite of loratadine, have been recently released for allergic rhinitis.. We sought to compare levocetirizine and desloratadine in a nasal provocation test (NPT) with grass pollen.. Twenty-four volunteers with grass pollen allergy and a history of rhinitis were enrolled in a double-blind, placebo-controlled, crossover study. Three NPTs were performed in a dose-escalating manner during the out-of-season period 4 hours after a single dose of levocetirizine (5 mg), desloratadine (5 mg), or placebo.. This study demonstrates a better overall protection of a single dose of levocetirizine compared with desloratadine in an NPT with grass pollen allergen. In contrast to late-phase inflammatory markers, which were unaffected, extravascular leakage of the early-phase marker albumin was significantly limited by levocetirizine.

Topics: Adult; Albumins; Allergens; Biomarkers; Cetirizine; Cross-Over Studies; Differential Threshold; Double-Blind Method; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Hypersensitivity; Loratadine; Male; Nasal Lavage Fluid; Nasal Provocation Tests; Piperazines; Poaceae; Pollen; Treatment Outcome

Allergic rhinitis is characterized by an IgE-dependent inflammation. Nasal obstruction is related to allergic inflammation. Some antihistamines have been demonstrated to be capable of improving this nasal symptom.. The aim of this pilot study was to evaluate nasal symptoms, nasal airflow, inflammatory cells, and cytokine pattern in patients with seasonal allergic rhinitis (SAR), before and after treatment with levocetirizine, desloratadine, or placebo.. Thirty patients with SAR were evaluated, 27 males and three females (mean age 26.9+/-5.4 years). All of them received levocetirizine (5 mg/day), desloratadine (5 mg/day), or placebo for 2 weeks. The study was double-blind, parallel-group, placebo-controlled, and randomized. Total symptom score (TSS) (including: rhinorrhea, nasal itching, sneezing, and nasal obstruction) was assessed before and after treatment. Rhinomanometry, nasal lavage, and nasal scraping were performed in all subjects before and after treatment. Inflammatory cells were counted by conventional staining; IL-4 and IL-8 were measured by immunoassay on fluids recovered from nasal lavage.. Levocetirizine treatment induced significant symptom relief (P=0.0009) and improved nasal airflow (P=0.038). Desloratadine also relieved TSS (P=0.01), but did not affect nasal airflow. Levocetirizine significantly reduced eosinophils (P=0.029), neutrophils (P=0.005), IL-4 (P=0.041), and IL-8 (P=0.02), whereas desloratadine diminished IL-4 only (P=0.044). Placebo treatment did not significantly affect any evaluated parameters.. This pilot study demonstrates the effectiveness of levocetirizine in: (i) relieving nasal symptoms, (ii) improving nasal airflow, (iii) reducing leucocyte infiltration, and (iv) diminishing cytokine levels. These findings are the first evidence of the effectiveness of levocetirizine in SAR.

Topics: Adult; Cetirizine; Double-Blind Method; Eosinophils; Female; Histamine H1 Antagonists; Humans; Interleukin-4; Interleukin-8; Leukocyte Count; Loratadine; Male; Nasal Lavage Fluid; Nasal Obstruction; Pilot Projects; Piperazines; Rhinitis, Allergic, Seasonal; Statistics, Nonparametric

Desloratadine (DL) and levocetirizine (LCZ) are the newest commercialized antihistamines. Pharmacokinetics, pharmacodynamics and clinical data are available for both drugs, but there is to date no direct comparison involving the nose and skin at the same time. We compared the effects of a single dose of the two drugs in the nose and skin over 24 h.. Twenty-three patients with symptomatic allergic rhinitis were enrolled in a randomized double-blind crossover administration of DL and LCZ. The histamine-induced wheal and flare was measured at baseline and 2 and 24 h after dosing. A reflective total symptom score (rTSS) for the previous 24 h was assessed before and after each dose. An instant symptom score was also measured at various time points after each drug.. LCZ provided greater inhibition of the flare at 2 h (p = 0.05) and at 24 h (p = 0.007) and greater inhibition of the wheal only at 2 h (p = 0.02). The decrease in wheal and flare was significant versus baseline (p = 0.007) with both drugs. The rTSS of the previous 24 h decreased significantly with both LCZ (11.53 vs. 8.0; p < 0.05) and DL (11.3 vs. 7.9; p < 0.05). The instant TSS progressively decreased in parallel with both drugs, but a difference in favor of LCZ was seen 2 h after dosing.. Single doses of DL and LCZ had a comparable effect on nasal symptoms, but LCZ was faster and displayed a greater effect on histamine wheal.

Topics: Adolescent; Adult; Cetirizine; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Male; Middle Aged; Nose; Piperazines; Rhinitis; Skin; Skin Tests; Treatment Outcome

Modern H(1)-antihistamines differ in their in vitro binding affinity, but their comparative in vivo bioactivity in asthmatic airways is unknown.. We compared clinically recommended doses of 3 H(1)-antihistamines on airway hyperresponsiveness to AMP challenge (the primary outcome variable).. Sixteen atopic patients with mild-to-moderate asthma of whom 10 were receiving inhaled corticosteroid therapy (all had positive results to house dust mite on skin prick testing) were randomized in a double-blind, placebo-controlled, cross-over fashion to receive single doses of 5 mg of desloratadine, 180 mg of fexofenadine hydrochloride (FEX), 5 mg of levocetirizine dihydrochloride (LEV), or placebo, with AMP challenge performed 12 hours after dosing.. All H(1)-antihistamines demonstrated significantly greater (P <.05) geometric mean +/- SEM AMP PC(20) values compared with that of placebo (86 +/- 29 mg/mL): desloratadine, 189 +/- 54 mg/mL; FEX, 176 +/- 57 mg/mL; and LEV, 163 +/- 48 mg/mL. Prechallenge forced expiratory flow at 25% to 75% of maximal lung volume (percent predicted) but not FEV(1) was significantly higher (P <.05) for all H(1)-antihistamines compared with that of placebo (53% +/- 4%): desloratadine, 62% +/- 4%; FEX, 62% +/- 4%; and LEV, 59% +/- 3%. There were no significant differences in either AMP PC(20) or lung function values among the H(1)-antihistamines.. Single doses of H(1)-antihistamines improved airway hyperresponsiveness and small-airways caliber to a similar degree. Data for in vitro binding affinity do not therefore translate into commensurate differences in in vivo bioactivity at clinically recommended doses.

Topics: Acetates; Adenosine Monophosphate; Adult; Aged; Asthma; Bronchial Provocation Tests; Cetirizine; Cross-Over Studies; Double-Blind Method; Female; Forced Expiratory Volume; Histamine H1 Antagonists; Humans; Loratadine; Male; Middle Aged; Piperazines; Respiratory Hypersensitivity; Terfenadine

Ligand residence time is thought to be a critical parameter for optimizing the in vivo efficacy of drug candidates. For the histamine H1 receptor (H1R) and other G protein-coupled receptors, the kinetics of ligand binding are typically measured by low throughput radioligand binding experiments using homogenized cell membranes expressing the target receptor. In this study, a real-time proximity assay between H1R and β-arrestin2 in living cells was established to investigate the dynamics of antihistamine binding to the H1R. No receptor reserve was found for the histamine-induced recruitment of β-arrestin2 to the H1R and the transiently recruited β-arrestin2 therefore reflected occupancy of the receptor by histamine. Antihistamines displayed similar kinetic signatures on antagonizing histamine-induced β-arrestin2 recruitment as compared to displacing radioligand binding from the H1R. This homogeneous functional method unambiguously determined the fifty-fold difference in the dissociation rate constant between mepyramine and the long residence time antihistamines levocetirizine and desloratadine.

Topics: beta-Arrestin 2; Binding, Competitive; Bioluminescence Resonance Energy Transfer Techniques; Cetirizine; Dose-Response Relationship, Drug; HEK293 Cells; Histamine; Histamine Agonists; Histamine H1 Antagonists, Non-Sedating; Humans; Kinetics; Ligands; Loratadine; Luciferases, Firefly; Models, Biological; NFATC Transcription Factors; Promoter Regions, Genetic; Protein Binding; Radioligand Assay; Receptors, Histamine H1; Recombinant Fusion Proteins

Chronic idiopathic urticaria (CIU) is not uncommon, yet there is little information about the clinical features of CIU patients in Taiwan. The purpose of this study was to investigate the clinical features of CIU in Taiwan.. Patients with CIU were collected consecutively from the Urticaria Special Clinic in a medical center in northern Taiwan from December 2005 to May 2006. Clinical features and laboratory findings were studied. We also evaluated the therapeutic response of CIU patients with second-generation H1 receptor antagonist monotherapy for 6 weeks.. A total of 62 CIU patients were investigated. The female to male ratio was 2.1:1 with a mean age of 31.8 years. The mean duration of the disease was 25.7 months (1.5-180 months). The most common aggravating factor was weather (79.7%), especially hot weather (50.8%). Fifty percent of the patients had atopy, and 37.3% of patients had positive autologous serum skin test. Besides, 61.3% of patients had at least one serum specific IgE antibody to the 18 common allergens examined. Finally, 60.7% of patients responded well to second-generation H1 receptor antagonist. Non-responders tended to have atopy (p = 0.0471), especially allergic rhinitis (p = 0.0107).. This study provided an overview of CIU patients in a medical center in northern Taiwan. We found that atopy did not influence the severity or durtation of CIU. Nevertheless, atopy was associated with a poor therapeutic response of second-generation antihistamine. A survey of personal atopy history, especially allergic rhinitis, is important for management of CIU patients in Taiwan.

Topics: Adolescent; Adult; Cetirizine; Chronic Disease; Female; Histamine H1 Antagonists; Humans; Loratadine; Male; Middle Aged; Taiwan; Treatment Outcome; Urticaria; Young Adult

Allergic rhinitis (AR) affects a large percentage of paediatric patients. With the wide array of available agents, it has become a challenge to choose the most appropriate treatment for patients. Second-generation antihistamines have become increasingly popular because of their comparable efficacy and lower incidence of adverse effects relative to their first-generation counterparts, and the safety and efficacy of this drug class are established in the adult population. Data on the use of the second-generation antihistamines oral cetirizine, levocetirizine, loratadine, desloratadine and fexofenadine, and the leukotriene receptor antagonist montelukast as well as azelastine nasal spray in infants and children are evaluated in this review. These agents have been found to be relatively safe and effective in reducing symptoms associated with AR in children. Alternative dosage forms such as liquids or oral disintegrating tablets are available for most agents, allowing ease of administration to most young children and infants; however, limited data are available regarding use in infants for most agents, except desloratadine, cetirizine and montelukast. Unlike their predecessors, such as astemizole and terfenadine, the newer second-generation antihistamines and montelukast appear to be well tolerated, with absence of cardiotoxicities. Comparative studies are limited to cetirizine versus ketotifen, oxatomide and/or montelukast. Although second-generation antihistamines and montelukast are deemed relatively safe for use in paediatric patients, there are some noteworthy drug interactions to consider when selecting an agent. Given the wide variety of available agents for treatment of AR in paediatric patients, the safety and efficacy data available for specific age groups, type of AR, dosage form availability and cost should be considered when selecting treatment for AR in infants and children.

Topics: Acetates; Administration, Oral; Adult; Anti-Allergic Agents; Anti-Asthmatic Agents; Astemizole; Cetirizine; Child; Cyclopropanes; Drug Administration Schedule; Drug Interactions; Histamine H1 Antagonists, Non-Sedating; Humans; Ketotifen; Leukotriene Antagonists; Loratadine; Piperazines; Quinolines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Safety; Sulfides; Tablets; Terfenadine; Treatment Outcome

Allergy is thought to be one of the etiologic factors in otitis media. The purpose of this study was to determine the histopathologic effects of H1 histamine receptor antagonists in an experimental histamine-induced middle ear inflammation model. In group A (20 rabbits), histamine challenge followed a 3-day intramuscular pretreatment with a single dose of 0.1 ml hydroxyzine hydrochloride (50 mg/ml) per day. In group B (20 rabbits), histamine challenge followed a 3-day pretreatment with a single dose 1.2 mg desloratadine per day orally. In group C (20 rabbits), histamine challenge followed a 3-day pretreatment with a single dose 1.2 mg levocetirizine per day orally. On the fourth day after baseline otomicroscopy 0.5 ml histamine 20 mg/ml was injected transtympanically on the right. Middle ear mucosa was removed and the following parameters were assessed: edema, vascular dilatation and congestion, inflammation, acute inflammatory component, presence of eosinophils, activity of the inflammation and fibrosis. A semi-quantitative grading system of 0-3 was used for grading of all parameters and statistical analysis performed by using the Mann-Whitney non-parametric test. Group A mucosae showed lower grades of all the parameters evaluated compared with those of group B. Histopathology of the mucosae of group C showed lower grade of inflammation compared with group B with significant statistical difference for the seven parameters tested. Our data validate the use of antihistamines in the treatment of refractory OME of allergic origin. Oldest H1 antagonists can be replaced by the newest agents who counteract successfully histamine effects, without any interactions or adverse effects from central nervous system.

Topics: Animals; Cetirizine; Disease Models, Animal; Ear, Middle; Female; Histamine H1 Antagonists, Non-Sedating; Loratadine; Male; Mucous Membrane; Otitis Media with Effusion; Rabbits

The predictive efficacy of drugs in humans is frequently estimated from both a high affinity for their receptor as measured in vitro and a long plasmatic half-life. This is grossly misleading since one key parameter is missing: drug concentration at the receptor site in vivo. As a case study we compared the efficacies of three H(1) antihistamines in inhibiting histamine-induced wheal and flare in humans at two different time points with the above mentioned parameters. It is concluded that estimating in vivo receptor occupancy, which takes into account both the affinity of the drug for the receptor and its free plasma concentration, is a far better predictor for human pharmacodynamics and hence antihistamine potency, than considering in vitro affinity and plasmatic half-life only.

Topics: Animals; Cetirizine; CHO Cells; Cricetinae; Cricetulus; Histamine H1 Antagonists; Humans; Loratadine; Piperazines; Predictive Value of Tests; Receptors, Histamine H1; Recombination, Genetic; Terfenadine; Urticaria

Topics: Cetirizine; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Nasal Obstruction; Nasal Provocation Tests; Piperazines; Rhinitis, Allergic, Perennial