The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Martin K Church - One of the best experts on this subject based on the ideXlab platform.
-
the inhibition by Levocetirizine and fexofenadine of the histamine induced wheal and flare response in healthy caucasian and japanese volunteers
Acta Dermato-venereologica, 2013Co-Authors: Nicole Schoepke, Martin K Church, Marcus MaurerAbstract:This randomized, double-blind, placebo-controlled cross over study compared inhibition by one 5 mg dose of Levocetirizine with two 60 mg doses of fexofenadine separated by 12 h of histamine-induced wheal and flare responses in 9 Caucasian and 9 Japanese healthy male volunteers. Levocetirizine was more inhibitory than fexo fenadine on wheal, flare and pruritus (p < 0.005). Variability, evaluated from the standard deviation of inhibition, ranged from 14% to 23.2% for Levocetirizine and 65.4% to 112.4% for fexofenadine. Levocetirizine had a faster onset of action (30–90 min versus 2 h), shorter time to maximum effect (3–4 versus 3–6 h) and longer duration of action (at least 24 h versus ~12 h) than fexofenadine. The plasma levels of Levocetirizine rose more quickly, reached higher levels, were more consistent and decreased slower than those of fexofenadine. There were
-
pharmacology of antihistamines
Indian Journal of Dermatology, 2013Co-Authors: Martin K Church, Diana S ChurchAbstract:H 1- antihistamines, the mainstay of treatment for urticaria, were developed from anticholinergic drugs more than 70 years ago. They act as inverse agonists rather than antagonists of histamine H 1 -receptors which are members of the G-protein family. The older first generation H 1- antihistamines penetrate readily into the brain to cause sedation, drowsiness, fatigue and impaired concentration and memory causing detrimental effects on learning and examination performance in children and on impairment of the ability of adults to work and drive. Their use should be discouraged. The newer second-generation H 1 -antihistamines are safer, cause less sedation and are more efficacious. Three drugs widely used for symptomatic relief in urticaria, desloratadine, Levocetirizine and fexofenadine are highlighted in this review. Of these Levocetirizine and fexofenadine are the most potent in humans in vivo . However, Levocetirizine may cause somnolence in susceptible individuals, whereas fexofenadine has a relatively short duration of action and may be required to be given twice daily for all round daily protection. Although desloratadine is less potent, it has the advantages of rarely causing somnolence and having a long duration of action.
-
the effectiveness of Levocetirizine and desloratadine in up to 4 times conventional doses in difficult to treat urticaria
The Journal of Allergy and Clinical Immunology, 2010Co-Authors: Maria Staevska, Todor A Popov, Tanya Kralimarkova, Cvetelina Lazarova, Steliana Kraeva, Dora Popova, Diana S Church, Vasil Dimitrov, Martin K ChurchAbstract:Background 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. Objective To provide supportive evidence for the European guidelines. Methods 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. Results 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: ∼15% of patients were good responders, ∼10% were nonresponders, and ∼75% were responders to higher than conventional antihistamine doses. No serious or severe adverse effects warranting discontinuation of treatment occurred with either drug. Conclusion 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.
-
the effectiveness of Levocetirizine and desloratadine in up to 4 times conventional doses in difficult to treat urticaria
The Journal of Allergy and Clinical Immunology, 2010Co-Authors: Maria Staevska, Todor A Popov, Tanya Kralimarkova, Cvetelina Lazarova, Steliana Kraeva, Diana S Church, Vasil Dimitrov, Martin K Church, D N PopovaAbstract:Background 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. Objective To provide supportive evidence for the European guidelines. Methods 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. Results 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: ∼15% of patients were good responders, ∼10% were nonresponders, and ∼75% were responders to higher than conventional antihistamine doses. No serious or severe adverse effects warranting discontinuation of treatment occurred with either drug. Conclusion 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.
-
a comparison of Levocetirizine and desloratadine in the histamine induced wheal and flare response in human skin in vivo
Inflammation Research, 2006Co-Authors: Todor A Popov, Vasil Dimitrov, D Dumitrascu, A Bachvarova, C Bocsan, Martin K ChurchAbstract:Background The histamine-induced wheal and flare response was used to compare quantitatively the antihistaminic potency of Levocetirizine and desloratadine.
Claus Bachert - One of the best experts on this subject based on the ideXlab platform.
-
a review of the efficacy of desloratadine fexofenadine and Levocetirizine in the treatment of nasal congestion in patients with allergic rhinitis
Clinical Therapeutics, 2009Co-Authors: Claus BachertAbstract:Abstract Background: 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. Objective: This review included nasal challenge studies and clinical trials that reported the effects on nasal congestion of the newer second-generation antihista-mines desloratadine, fexofenadine, and Levocetirizine. Methods: 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 levoce-tirizine for nasal congestion associated with AR were excluded. Results: 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 levocetiri-zine 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 P ≤ 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 P ≤ 0.005). Conclusions: 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.
-
Levocetirizine improves health related quality of life and health status in persistent allergic rhinitis
Respiratory Medicine, 2006Co-Authors: Walter G Canonica, Claus Bachert, Jean Bousquet, J. Mullol, S R Durham, Ludger Klimek, Genevieve Van Hammee, Paul Van CauwenbergeAbstract:Summary Background Allergic rhinitis is a chronic respiratory disorder with a detrimental impact on health-related quality of life (HRQOL) and health status. Enhancement and maintenance of patient function and well-being are therefore considered as essential. Objective To determine whether long-term treatment with Levocetirizine 5 mg improves HRQOL and health status in persistent allergic rhinitis (PER) patients assessed with RQLQ and SF-36 scales over a 6-month period. Methods The Xyzal® in PER Trial (XPERT™) was a multi-center, double-blind, parallel-group study. A total of 551 patients were randomized to receive Levocetirizine 5 mg or placebo once daily for 6 months and assessed for symptoms, HRQOL (Rhinoconjunctivitis Quality of Life Questionnaire: RQLQ) and health status (SF-36). Sensitivity of the RQLQ and SF-36 to disease severity was tested to ensure their suitability for use in PER patients. Treatment effect was assessed by means of repeated measures analyses. Results Over the 6-month treatment period, Levocetirizine showed statistically significant improvements over placebo in HRQOL ( P 0.001 for all RQLQ domains and overall scores) and health status ( P ⩽ 0.004 for SF-36 physical and mental summary scores; P 0.05 for all SF-36 scales). The relative improvement of Levocetirizine over placebo exceeded the predefined clinically meaningful threshold of 30% for all RQLQ scores and the improvement from baseline was 3 times the established MID for RQLQ. Conclusion The RQLQ and SF-36 could be used to measure HRQOL and health status in PER patients. Long-term treatment with Levocetirizine provides sustained improvement of HRQOL and reduces disease burden in PER patients.
-
pathophysiology of nasal obstruction and meta analysis of early and late effects of Levocetirizine
Clinical & Experimental Allergy, 2006Co-Authors: Joke Patou, H De Smedt, P Van Cauwenberge, Claus BachertAbstract:Nasal obstruction, also referred to as congestion, blockage or stuffiness, is a crucial symptom in allergic rhinitis (AR) and may affect sleep as well as quality of life. Early- and late-phase-allergic reactions both contribute to nasal obstruction, although it primarily represents a major symptom in the chronic allergic reaction. A complex network of inflammatory and neurogenic phenomena relates to chronic nasal obstruction, including the subepithelial accumulation of inflammatory cells, particularly mast cells and eosinophils, and the release of neuropeptides. Nasal obstruction is a difficult-to-treat symptom. Vasoconstrictors (decongestants) and intranasal corticosteroids, due to their anti-inflammatory properties, have mainly been used for relieving the nasal passages from the congested mucosa. However, there is accumulating evidence recently that the latest-generation potent antihistamines have decongestant properties in AR. This paper aims to review the pathophysiologic background of nasal obstruction and the evidence for an antihistamine, Levocetirizine, in relieving nasal congestion. A meta-analysis on the early and late effects of Levocetirizine on nasal obstruction under artificial and natural allergen exposure conditions is presented, demonstrating convincingly that Levocetirizine shows a consistent effect on nasal obstruction as early as over the first 2 h and sustained over 6 weeks.
-
management of persistent allergic rhinitis evidence based treatment with Levocetirizine
Therapeutics and Clinical Risk Management, 2005Co-Authors: J. Mullol, Claus Bachert, Jean BousquetAbstract:Allergic rhinitis (AR) is a major health problem that can significantly impair quality of life (QoL). The former classification of AR comprises seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR), which do not adequately reflect the clinical course and presentation of AR. The Allergic Rhinitis and its Impact on Asthma (ARIA) classification is based on the duration of symptoms and their severity. Persistent AR (PER) is experienced for periods longer than 4 days/week and for more than 4 consecutive weeks, and may feature mild or moderate-to-severe disease based on the impairment of QoL and symptom severity. Oral antihistamines are a standard treatment option in AR. New second generation antihistamines have a rapid onset of action, are highly effective on AR symptoms, and some were even shown to relieve nasal congestion. Levocetirizine is a potent histamine H 1 -receptor antagonist with proven efficacy in both SAR and PAR, and it is the best studied therapeutic option in persistent AR. The Xyzal in Persistent Rhinitis Trial (XPERT™) studied 551 patients with PER, showing that Levocetirizine (5 mg/day compared with placebo) significantly improved nasal symptoms as early as the first week and for the 6 months of study, with significant improvement in nasal congestion after 6 weeks of treatment. Levocetirizine also improved QoL, was well tolerated, and produced substantial societal and employer cost savings. Thus, Levocetirizine is the first tested standard treatment for PER using ARIA classification, and shows prompt short-term and long-term relief of symptoms, improves patients' QoL, and provides economic benefits to employers and the society.
-
Levocetirizine improves quality of life and reduces costs in long term management of persistent allergic rhinitis
The Journal of Allergy and Clinical Immunology, 2004Co-Authors: Claus Bachert, Jean Bousquet, J. Mullol, Walter G Canonica, S R Durham, Ludger Klimek, Paul Van Cauwenberge, Genevieve Van HammeeAbstract:Background Allergic Rhinitis and its Impact on Asthma in collaboration with the World Health Organization initiative reclassified allergic rhinitis, like asthma, by duration and severity. The Xyzal in Persistent Rhinitis Trial is the first large, long-term clinical trial studying patients with persistent rhinitis as defined by Allergic Rhinitis and its Impact on Asthma. Objectives Two primary objectives were defined: comparison of the Rhinoconjunctivitis Quality of Life Questionnaire overall score and Total 5 Symptoms Score (rhinorrhea, sneezing, nasal congestion, and nasal and ocular pruritus) over a period of 4 weeks between Levocetirizine 5 mg and placebo. Secondary endpoints included similar evaluations at 1 week and 3, 4.5, and 6 months, summary scores for a general health status questionnaire (Medical Outcomes Survey Short Form 36), a pharmacoeconomic assessment, comorbidities, and a safety evaluation. Methods The Xyzal in Persistent Rhinitis Trial was a 6-month double-blind, placebo-controlled, multicenter, multinational trial in 551 patients. Adults with persistent rhinitis sensitized to both grass pollen and house dust mite were randomized to receive Levocetirizine 5 mg/d or placebo. Results A total of 421 patients completed the full study. Levocetirizine significantly improved both the Rhinoconjunctivitis Quality of Life Questionnaire overall score and the Total 5 Symptoms Score from week 1 to 6 months (all P values Conclusion Levocetirizine was shown to improve quality of life and symptoms and to decrease the overall costs of the disease over the 6-month treatment period.
Pawel Gorski - One of the best experts on this subject based on the ideXlab platform.
-
use of montelukast alone or in combination with desloratadine or Levocetirizine in patients with persistent allergic rhinitis
American Journal of Rhinology & Allergy, 2011Co-Authors: Maciej Ciebiada, Tomasz Kmiecik, Malgorzata Gorskaciebiada, Marcin Barylski, Pawel GorskiAbstract:BackgroundWe assessed the course of treatment in patients with persistent allergic rhinitis (AR) treated with montelukast, Levocetirizine, or desloratadine alone or combinations of antihistamine an...
-
quality of life in patients with persistent allergic rhinitis treated with montelukast alone or in combination with Levocetirizine or desloratadine
Journal of Investigational Allergology and Clinical Immunology, 2008Co-Authors: Tomasz Kmiecik, Maciej Ciebiada, L M Dubuske, Pawel GorskiAbstract:■ Abstract Background: Persistent allergic rhinitis often impairs quality of life. Objective: We assessed the extent to which treating persistent allergic rhinitis with montelukast, desloratadine, and Levocetirizine alone or in combination improved quality of life. Methods: 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. Results: 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). Conclusions: Placebo, montelukast, desloratadine and Levocetirizine signifi cantly improved quality of life. Combining montelukast with either Levocetirizine or desloratadine gave additional benefi ts in comparison to each agent alone and could be considered for patients whose quality of life is impaired by persistent allergic rhinitis.
-
montelukast with desloratadine or Levocetirizine for the treatment of persistent allergic rhinitis
Annals of Allergy Asthma & Immunology, 2006Co-Authors: Maciej Ciebiada, L M Dubuske, Malgorzata Gorskaciebiada, Pawel GorskiAbstract:Background 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. Objective To investigate the effects of 6 weeks of treatment of persistent AR with desloratadine, Levocetirizine, or montelukast alone or in combination. Methods A randomized, double-blind, placebocontrolled 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. Results 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. Conclusions For persistent AR, the combination of montelukast and either desloratadine or Levocetirizine is more effective than monotherapy with these agents.
Pierre Chatelain - One of the best experts on this subject based on the ideXlab platform.
-
peripheral and central h1 histamine receptor occupancy by Levocetirizine a non sedating antihistamine a time course study in the guinea pig
British Journal of Pharmacology, 2007Co-Authors: Anubha Gupta, Michel Gillard, R Massingham, Pierre Chatelain, Bernard Christophe, Margarete HammarlundudenaesAbstract:BACKGROUND AND PURPOSE: The H(1) receptor occupancy (H1RO) in brain is an indicator of central side effects of antihistamines. Here, we determined the kinetics of central and peripheral H1RO by Levocetirizine in relation to its brain and plasma concentration, and investigated the role of the blood-brain barrier in any delay in brain H1RO. EXPERIMENTAL APPROACH: Concentration-time profiles in plasma and brain were obtained after 0.1 and 1 mg kg(-1) oral doses of Levocetirizine in guinea pigs. H1RO in brain was measured ex vivo using [3H]-mepyramine and, in the periphery, by measuring the degree of inhibition of histamine-induced contractions of isolated guinea pig ileum. KEY RESULTS: The concentration-time profile of Levocetirizine indicated lower levels (partition coefficient, K(p)=0.06-0.08), higher t(max) (2-4 h vs 1-1.5 h) and longer terminal half-life (4-5.6 h vs 2.1-2.8 h) in brain than plasma. The H1RO at 0.1 and 1 mg kg(-1) were 75% and 97%, respectively, at 1 hr in the periphery and, in the brain, were <20% and 28-67% respectively, at all time points studied. Brain H1RO vs plasma concentrations profile showed a delay, but not when compared to brain concentrations. CONCLUSIONS AND IMPLICATIONS: This study demonstrates an effective peripheral antihistamine effect of Levocetirizine without central adverse effects at the dose close to human therapeutic dose. The slow increase in H1RO in the brain with time was caused by slow blood-brain barrier transport of Levocetirizine. This demonstrates the importance of measuring time course of brain H1RO in relation to brain concentrations of drugs.
-
binding characteristics of cetirizine and Levocetirizine to human h1 histamine receptors contribution of lys191and thr194
Molecular Pharmacology, 2002Co-Authors: Michel Gillard, Christy Van Der Perren, Nicole Moguilevsky, R Massingham, Pierre ChatelainAbstract:Competition experiments with [3H]mepyramine showed that cetirizine and its enantiomers, Levocetirizine and (S)-cetirizine, bound with high affinity and stereoselectivity to human H1 histamine receptors (Ki values of 6, 3, and 100 nM, respectively). Cetirizine and Levocetirizine were 600-fold more selective for H1 receptors compared with a panel of receptors and channels. Binding results indicated that the interaction between cetirizine, its enantiomers, and histamine is compatible with a competitive behavior, in contrast with the noncompetitive profile of cetirizine and Levocetirizine observed in isolated organs. Binding kinetics provided a suitable explanation for this observation, because Levocetirizine dissociated from H1 receptors with a half-time of 142 min; that of (S)-cetirizine was only 6 min, implying that the former could act as a pseudo-irreversible antagonist in functional studies. The carboxylic function of Levocetirizine seemed responsible for its long dissociation time. Indeed, hydroxyl or methyl ester analogs dissociated more rapidly from H1 receptors, with half-times of 31 min and 7 min, respectively. The importance of the carboxylic function of Levocetirizine for the interaction with the H1 receptor was further supported by the results from the mutation of Lys191 to Ala191. This mutation decreased the dissociation half-time of Levocetirizine from 142 to 13 min and reduced its affinity from 3 to 12 nM, whereas the affinity and dissociation kinetics of hydroxyl and methyl ester analogs were hardly affected. The mutation of Thr194 reduced the binding stereoselectivity by selectively enhancing the affinity of the distomer.
-
binding characteristics of cetirizine and Levocetirizine to human h1 histamine receptors contribution of lys191 and thr194
Molecular Pharmacology, 2002Co-Authors: Michel Gillard, Christy Van Der Perren, Nicole Moguilevsky, R Massingham, Pierre ChatelainAbstract:Competition experiments with [3H]mepyramine showed that cetirizine and its enantiomers, Levocetirizine and (S)-cetirizine, bound with high affinity and stereoselectivity to human H1 histamine receptors (Ki values of 6, 3, and 100 nM, respectively). Cetirizine and Levocetirizine were 600-fold more selective for H1 receptors compared with a panel of receptors and channels. Binding results indicated that the interaction between cetirizine, its enantiomers, and histamine is compatible with a competitive behavior, in contrast with the noncompetitive profile of cetirizine and Levocetirizine observed in isolated organs. Binding kinetics provided a suitable explanation for this observation, because Levocetirizine dissociated from H1 receptors with a half-time of 142 min; that of (S)-cetirizine was only 6 min, implying that the former could act as a pseudo-irreversible antagonist in functional studies. The carboxylic function of Levocetirizine seemed responsible for its long dissociation time. Indeed, hydroxyl or methyl ester analogs dissociated more rapidly from H1 receptors, with half-times of 31 min and 7 min, respectively. The importance of the carboxylic function of Levocetirizine for the interaction with the H1 receptor was further supported by the results from the mutation of Lys191 to Ala191. This mutation decreased the dissociation half-time of Levocetirizine from 142 to 13 min and reduced its affinity from 3 to 12 nM, whereas the affinity and dissociation kinetics of hydroxyl and methyl ester analogs were hardly affected. The mutation of Thr194 reduced the binding stereoselectivity by selectively enhancing the affinity of the distomer.
Maciej Ciebiada - One of the best experts on this subject based on the ideXlab platform.
-
use of montelukast alone or in combination with desloratadine or Levocetirizine in patients with persistent allergic rhinitis
American Journal of Rhinology & Allergy, 2011Co-Authors: Maciej Ciebiada, Tomasz Kmiecik, Malgorzata Gorskaciebiada, Marcin Barylski, Pawel GorskiAbstract:BackgroundWe assessed the course of treatment in patients with persistent allergic rhinitis (AR) treated with montelukast, Levocetirizine, or desloratadine alone or combinations of antihistamine an...
-
quality of life in patients with persistent allergic rhinitis treated with montelukast alone or in combination with Levocetirizine or desloratadine
Journal of Investigational Allergology and Clinical Immunology, 2008Co-Authors: Tomasz Kmiecik, Maciej Ciebiada, L M Dubuske, Pawel GorskiAbstract:■ Abstract Background: Persistent allergic rhinitis often impairs quality of life. Objective: We assessed the extent to which treating persistent allergic rhinitis with montelukast, desloratadine, and Levocetirizine alone or in combination improved quality of life. Methods: 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. Results: 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). Conclusions: Placebo, montelukast, desloratadine and Levocetirizine signifi cantly improved quality of life. Combining montelukast with either Levocetirizine or desloratadine gave additional benefi ts in comparison to each agent alone and could be considered for patients whose quality of life is impaired by persistent allergic rhinitis.
-
montelukast with desloratadine or Levocetirizine for the treatment of persistent allergic rhinitis
Annals of Allergy Asthma & Immunology, 2006Co-Authors: Maciej Ciebiada, L M Dubuske, Malgorzata Gorskaciebiada, Pawel GorskiAbstract:Background 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. Objective To investigate the effects of 6 weeks of treatment of persistent AR with desloratadine, Levocetirizine, or montelukast alone or in combination. Methods A randomized, double-blind, placebocontrolled 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. Results 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. Conclusions For persistent AR, the combination of montelukast and either desloratadine or Levocetirizine is more effective than monotherapy with these agents.