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P. Rosenzweig - One of the best experts on this subject based on the ideXlab platform.
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pharmacokinetic and pharmacodynamic modeling of Mizolastine in healthy volunteers with an indirect response model
Clinical Pharmacology & Therapeutics, 2000Co-Authors: Claire Deschamps, Catherine Dubruc, P. RosenzweigAbstract:Objective The aim of this work was to model the pharmacokinetic and pharmacodynamic relationship of Mizolastine, a new H1-receptor antagonist obtained from histamine-induced wheal and flare inhibition test. Methods Fifteen healthy volunteers participated in this double-blind crossover study and randomly received single doses of 5, 10, 15, and 20 mg of Mizolastine and placebo at 1 week intervals. Simultaneous histamine tests and blood samples were performed before and at 9 different times up to 24 hours after each dosing. Pharmacokinetic and pharmacodynamic modeling were performed subject by subject for the 4 doses altogether by nonlinear regression. First, plasma concentrations were fit according to a two-compartment open model with zero order absorption and first order elimination. Then an indirect response model with inhibition of the formation rate was developed to describe the pharmacodynamic relationships between flare or wheal raw areas and plasma concentrations with the use of the pharmacokinetic parameters that were previously estimated. Results Mizolastine dose dependently inhibited the histamine-induced wheal and flare formation with a submaximum effect attained after 10 mg. The mean values of the pharmacodynamic parameters of apparent zero-order rate constant for the flare or wheal spontaneous appearance (kin), the first-order rate constant for the flare or wheal disappearance, the Mizolastine concentration that produced 50% suppression of the maximum attainable inhibition of kin, and the maximum attainable inhibition of the effect production were 14.1 cm2/h (coefficient of variation [CV], 32%), 0.68 h−1 (CV, 24%), 21.1 ng/mL (CV, 77%), and 0.92 (CV, 8%), respectively, for the flare and 1.9 cm2/h (CV, 64%), 0.63 h−1 (CV, 39%), 43.9 ng/mL (CV, 68%), and 0.87 (CV, 12%), respectively, for the wheal inhibition. Conclusion Pharmacokinetic and pharmacodynamic relationships of Mizolastine were reliably described with the use of an indirect pharmacodynamic model; this led to an accurate prediction of the pharmacodynamic activity of Mizolastine. (Clin Pharmacol Ther 2000;68:647-57.) Clinical Pharmacology & Therapeutics (2000) 68, 647–657; doi: 10.1067/mcp.2000.112341
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lack of behavioural toxicity of Mizolastine a review of the clinical pharmacology studies
Clinical & Experimental Allergy, 1999Co-Authors: P. Rosenzweig, A. PatatAbstract:First-generation H1 antihistamines were associated with major sedative side-effects which were heavily disruptive to young active and aged patients when performing everyday activities. Mizolastine is a potent and selective H1-receptor antagonist which slowly penetrates into the brain and thus lacks the sedative effects of earlier antihistamines. In this paper we present an overview of five clinical pharmacology studies which were carried out with a view to assessing Mizolastine effects on psychomotor and skilled performances, and on cognitive functions in young and aged subjects. The studies were all randomized, double-blind, placebo and (with the exception of one) active-drug controlled, cross-over studies. A total of 76 young and 15 aged subjects were enrolled. Two studies evaluated Mizolastine over a range of doses (5-45 mg), and three involved a single or multiple administrations of the therapeutic dose (10 mg/day). Comparators were first generation (clemastine, tripolidine) and second generation (terfenadine, cetirizine) antihistamines. Drug effects were evaluated through standardized psychometric and memory tests, and subjective self-ratings (visual analogue scales). In two studies, driving performance was assessed using an actual driving test. Two studies investigated drug interaction with depressants of the central nervous system such as alcohol and lorazepam. The results of the five reported studies were consistent in that Mizolastine showed to be free from sedative effects when administered at the therapeutic dose. As with other newly developed antihistamines, some changes occurred at higher dose levels. At the therapeutic dose Mizolastine did not alter driving performance and did not potentiate the depressant effects of alcohol and lorazepam. Mizolastine was shown to be free from sedative effects that could affect the safe performance of everyday life activities in young and aged patients when administered at the therapeutic dose. Language: en
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study of cardiac repolarization in healthy volunteers performed with Mizolastine a new h1 receptor antagonist
British Journal of Clinical Pharmacology, 1999Co-Authors: S Chaufour, C Deschamps, Henri Caplain, C Dubruc, N Lilienthal, C Lheritier, P. RosenzweigAbstract:Aims The occurence of serious dysrhythmias, such as torsades de pointes, with terfenadine and astemizole had led to a reexamination of the potential effect of H1 antihistamines on cardiac repolarization. Mizolastine is a potent, selective, nonsedating peripherally acting H1-receptor antagonist which is registered for rhinitis and urticaria at a recommended dose of 10 mg once daily. The present study was carried out to investigate the effects of therapeutic and supratherapeutic doses of Mizolastine, on ventricular repolarization in healthy volunteers. Methods Twenty-four healthy young volunteers participated in a double-blind, placebo-controlled, randomised study with three parallel groups. Each group consisted of 2 way cross-over 7 day treatment periods where Mizolastine (10, 20 or 40 mg) and placebo were randomly administered. On day 1 and day 7, 12-lead ECG recordings were performed prior and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 20 h after dosing and from day 2 to day 6, before dosing and 1, 2, 3, and 4 h after. Results Whatever the analysis used (raw data, changes from baseline, incidence of individual out-of-range values) no significant differences were observed at any dose level vs placebo, on any of ECG parameters (HR, PR, QRS, QT, and QTc). In particular, no effect of Mizolastine vs placebo was shown on QT and QTc although 95% CIs were wide. The only subject who exhibited a QTc≥450 ms received placebo for 7 days. Conclusions This study found no evidence of an effect of Mizolastine up to 40 mg (four times the therapeutic dose) on ventricular repolarization in healthy volunteers.
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lack of effect of Mizolastine on the safety and pharmacokinetics of digoxin administered orally in repeated doses to healthy volunteers
International Journal of Clinical Pharmacology and Therapeutics, 1998Co-Authors: S Chaufour, Catherine Dubruc, Le Coz F, T Denolle, I Cimarosti, C Deschamps, N Ulliac, B Delhotallandes, P. RosenzweigAbstract:Abstract The effects of mizolatine, a new H1 receptor antagonist, on safety and pharmacokinetics of digoxin were studied in a double-blind placebo-controlled crossover study. After administration of digoxine alone (0.25 mg o.d. for 7 days), 12 healthy young male volunteers (23+/-2 years) received either placebo and digoxin (0.25 mg o.d.) or Mizolastine (10 mg o.d.) and digoxin (0.25 mg o.d.) during 7 days. The assessment criteria consisted in hemodynamic and ECG parameters recordings and the pharmacokinetics of digoxin during the last day of coadministration (day 14). No difference between the 2 treatment groups was evidenced on ECG, hemodynamic, and clinical and laboratory safety parameters. No change in AUC and tmax was recorded. No clinically relevant effect of Mizolastine on the digoxin pharmacokinetics was found. However, a statistically significant increase in digoxin Cmax (3.03+/-0.18 nmolxl(-1) vs 2.52+/-0.19 nmolxl(-1), p < 0.05) and Cmin (0.99+/-0.08 nmolxl(-1) vs 0.87+/-0.07 nmolxl(-1), p=0.05) occurred after the coadministration vs digoxin alone. It can be concluded that Mizolastine and digoxin at therapeutic dosages can be safely coadministered.
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inhibition of histamine induced skin wheal and flare after 5 days of Mizolastine
The Journal of Clinical Pharmacology, 1996Co-Authors: Jeanlouis Pinquier, Catherine Dubruc, Henri Caplain, Mariejosee Cabanis, Aline Stallabourdillon, P. RosenzweigAbstract:Mizolastine is a new, nonsedating antihistamine providing satisfactory symptomatic relief in allergic rhinitis and urticaria. The purpose of this study was to use inhibition of wheal and flare formation after 2-mu g intradermal histamine injections as a measure of the antihistamine effect of repeated doses of Mizolastine. Eight volunteers were enrolled in this four-arm, double-blind, cross-over, randomized study. Three dose levels of once-daily Mizolastine (5 mg, 10 mg, and 15 mg) were compared with placebo during 5-day dose periods. Histamine tests were performed before drug intake on days 1 and 5, and then 2, 3, 4, 6, 8, 10, 12, 14, and 24 hours after drug intake on day 5. All 3 doses of Mizolastine were more effective than placebo in suppressing wheal and flare reactions, and the antihistamine activity was highest at both the 10- and 15-mg dose levels. The effect on the flare reaction appeared within 1 hour, reached a maximum effect 4 hours after administration, and persisted for as long as 24 hours. The relative changes in wheal and flare areas were correlated with Mizolastine trough plasma levels on day 5. Safety was satisfactory in all groups. This study confirms that Mizolastine is a rapid and potent antihistamine; and its long-lasting effectiveness indicates that a once-daily regimen is acceptable for clinical use.
Francisque Leynadier - One of the best experts on this subject based on the ideXlab platform.
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Mizolastine in primary acquired cold urticaria
Journal of The American Academy of Dermatology, 2003Co-Authors: Louis Dubertret, Catherine Pecquet, Margarita Murrietaaguttes, Francisque LeynadierAbstract:Abstract Background: Treatment of primary acquired cold urticaria (CU) is quite difficult because of variable clinical effectiveness and side effects of classic antihistamines. Objective: The objective of the study was to assess the efficacy and safety of Mizolastine, an antihistaminic with antiallergic properties, versus placebo in primary acquired CU. Methods: This study was a phase II, multicenter, randomized, double-blind, crossover, placebo-controlled study of Mizolastine (10 mg, once daily) versus placebo in 28 patients with primary acquired CU. Efficacy was measured by the cold-stimulation time test, the wheal response, and pruritus intensity after an ice-cube test. Results: Mizolastine delayed the cold-induced wheal reaction, reduced wheal response at 3 and 10 minutes, and reduced pruritus intensity. Statistically significant differences were observed versus placebo for the cold-stimulation time test, wheal response at 3 and 10 minutes, and pruritus intensity ( P = .006, .015, .009, and .005, respectively). No clinically relevant adverse events were reported. Conclusions: Mizolastine (10 mg, once daily) was shown to be superior to placebo for both delaying and reducing the cold-induced wheal reaction without significant adverse events. Results suggest that Mizolastine may be effective in the treatment of CU. (J Am Acad Dermatol 2003;48:578-83.)
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Mizolastine provides effective symptom relief in patients suffering from perennial allergic rhinitis a double blind placebo controlled study versus loratadine
Annals of Allergy Asthma & Immunology, 2002Co-Authors: Charles Freche, Francisque Leynadier, Claus Bachert, F Horak, David W Hide, Fernando Duce Gracia, Manfred Goos, Attila Horvath, Eva Antosova, Muriel VerrecchiaAbstract:Background Mizolastine is a nonsedating H 1 histamine receptor antagonist with additional antiallergic properties currently marketed in Europe for the treatment of seasonal and perennial allergic rhinitis (PAR) and urticaria. Objective This multicenter, randomized, double-blind, parallel-group study was conducted to evaluate the efficacy and safety of Mizolastine in PAR compared with loratadine and placebo. Methods After a 1-week placebo run-in period, 428 adult PAR patients received placebo (146 of 428), Mizolastine 10 mg (141 of 428), or loratadine 10 mg (141 of 428) once daily for 28 days. Symptoms were evaluated by patients and physicians using a total nasal score, evaluating itching, rhinorrhea, nasal blockade, and sneezing severity. Results Mizolastine treatment resulted in a significantly greater decrease in patient-rated total nasal score than placebo after 2 weeks (D14; −42%, P P = 0.01), and significantly greater than that observed with loratadine at D14 ( P = 0.031). No significant difference in change in total nasal score was observed between loratadine and placebo at 2- and 4-week visits. The global safety was satisfactory and the incidence of adverse events was similar in the three treatment groups. Conclusions Mizolastine provides effective symptom relief in PAR together with a satisfactory safety profile. Improvement with Mizolastine was significantly greater than placebo throughout the study despite a large placebo effect. Also Mizolastine's effects were greater those observed with loratadine after 2 weeks of treatment.
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efficacy and safety of Mizolastine in seasonal allergic rhinitis
Annals of Allergy Asthma & Immunology, 1996Co-Authors: Francisque Leynadier, J Bousquet, Margarita Murrieta, Pierre AttaliAbstract:Background Mizolastine is a new, nonsedating antihistamine under clinical investigation for treatment of allergic rhinitis and urticaria. Objective The purpose of this study was to determine the optimally active dose of once-daily Mizolastine in seasonal allergic rhinitis. Methods This multicenter, double-blind, parallel study involved 494 patients randomly allocated to Mizolastine (5, 10, or 15 mg) or placebo for 2 weeks. Results Physicians' assessments indicated the superiority of 10 and 15 mg Mizolastine to placebo in reducing total symptom scores (P = .002), nasal scores ( P = .004), and ocular scores (P = .007) at day 7. Patients' diaries showed a significant change from baseline in daily symptom scores as early as day 2 (P = .01) in 10- and 15-mg Mizolastine groups in comparison to placebo, but this was not maintained throughout the study. No additional benefits were demonstrated during the second week of treatment in terms of efficacy. Adverse events were slightly more frequent in the 15-mg Mizolastine group. Conclusion This study confirms Mizolastine is an effective and well tolerated antihistamine in the treatment of seasonal allergic rhinitis; 10 mg is the optimal dose.
M Murrieta - One of the best experts on this subject based on the ideXlab platform.
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comparative therapeutic effect and safety of Mizolastine and loratadine in chronic idiopathic urticaria urtilor study group
European Journal of Dermatology, 2000Co-Authors: F Leynadier, C Duarterisselin, M MurrietaAbstract:Mizolastine, a new second-generation H1 receptor antagonist with additional anti-allergic properties, was compared with loratadine in 61 patients suffering from severe chronic idiopathic urticaria (CIU). In this double-blind study, patients were randomly allocated to receive either Mizolastine 10 mg (n = 26) or loratadine 10 mg (n = 35) once-daily for 28 days. Both compounds were well tolerated, safe and efficacious. The reduction in the number of episodes per week (5. 6+/-16.3 and 6.4+/-12.4 for Mizolastine and loratadine, respectively) and the reduction in the symptom severity score, measured using a Visual Analogue Scale (VAS), were comparable (30.2 +/- 39.0 mm and 30.5 +/- 28.5 mm for Mizolastine and loratadine, respectively). Mizolastine had a positive effect on angioedema (85% CI 95% [0.69-1.00]) of patients improved compared with 75% (CI 95% [0.59-0.91]) of the loratadine group and the differential reduction of the mean total duration of episodes in the Mizolastine group was higher when compared with the loratadine group (from 13.7 +/- 33.5 hours on day 0 to 5.1 +/- 9.0 hours over the treatment period and from 8.2 +/- 8.8 hours on day 0 to 5.1 +/- 7.8 hours over the treatment period for Mizolastine and loratadine, respectively). Prick test analysis demonstrated that both drugs caused a significant decrease of histamine-induced wheal and flare with no development of tolerance, with a significant superiority of Mizolastine over loratadine for some histamine concentrations. Mizolastine and loratadine both proved very efficacious and safe. In addition Mizolastine demonstrated a superiority in prick tests, beneficial effects on angioedema and seemed to provide a faster onset of action.
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qt interval monitoring during clinical studies with Mizolastine a new h1 antihistamine
Clinical & Experimental Allergy, 1999Co-Authors: M C Delauchecavallier, S Chaufour, M Murrieta, E Guerault, A Lacroux, A WajmanAbstract:Background Some H1 antihistamines are at risk for rare but severe dysrhythmias due to an effect on the ventricular repolarization. Objective To present an overview of the QT interval monitoring performed during the clinical development of Mizolastine, a new selective second-generation H1 antihistamine. Methods The ECGs database analysis of clinical studies conducted in volunteers and patients is summarized and focused on the results of reported studies and studies specifically designed for the assessment of the effect of Mizolastine on cardiac repolarization, through the QT interval measurements. Mizolastine was orally administered up to 75 mg single dose and 40 mg repeated dose in healthy volunteers (i.e. 7.5 and 4 times the recommended dose, respectively) and at a dose of 10 or 15 mg in patients. Results In healthy volunteers, no increased incidence of QTc values >440 msec or ΔQTc ≥40 msec were recorded compared to placebo. No dose-related increase in QTc interval was observed. The ECG parameters were not modified by the co-administration of Mizolastine with digoxin, diltiazem and erythromycin, when compared to the effect of each co-administered drug alone. In patients, the mean QTc interval changes from baseline did not significantly differ from placebo. In comparative studies vs. loratadine a similar incidence of out of range values was observed with Mizolastine and loratadine. Conclusion ECG monitoring of volunteers and patients included in clinical studies conducted with Mizolastine showed no significant effect of Mizolastine on cardiac repolarization.
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Mizolastine therapy also has an effect on nasal blockade in perennial allergic rhinoconjunctivitis
Allergy, 1998Co-Authors: Claus Bachert, Jonathan Brostoff, G Scadding, J Tasman, A Stallabourdillon, M MurrietaAbstract:Background Mizolastine is a new, nonsedating antihistamine with additional anti-inflammatory properties, providing relief in allergic rhinitis and urticaria. The aim of this study was to determine the efficacy and safety of 10 mg o.d. Mizolastine given to patients with perennial allergic rhinoconjunctivitis. Methods This double-blind, placebo-controlled study involved 257 patients suffering from the disease for more than 10 years. They were allocated, after a 1-week placebo run-in, to receive Mizolastine (n = 133) or placebo (n = 124) for 4 weeks. Results Mizolastine-treated patients showed significantly greater alleviation of nasal symptoms, with a mean decrease of 36% compared with pretreatment score, compared to a mean decrease of 10% in placebo patients (P<0.001). Nasal blockade responded favorably to Mizolastine compared to placebo and was associated with a significant reduction in rhinoscopy findings (P=0.030). Likewise, the mean ocular symptom score decreased 40% in Mizolastine-treated patients compared to 7% in the placebo group (P<0.003). The safety profile of Mizolastine was satisfactory and similar to that of placebo. Conclusions In patients suffering from perennial allergic rhinoconjunctivitis, Mizolastine is a safe and potent treatment. Mizolastine's pronounced effect on nasal blockade could possibly be linked to its anti-inflammatory properties.
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lack of subsensitivity to Mizolastine over 8 week treatment
Allergy, 1996Co-Authors: J Bousquet, M Murrieta, I Chanal, A StallabourdillonAbstract:Mizolastine is a new, nonsedating antihistamine providing satisfactory symptom relief in allergic rhinitis and urticaria. The purpose of this study was to use the wheal and flare skin reactions model to assess the maintenance of the pharmacodynamic effect of Mizolastine, administered for 2 months. This double-blind, parallel-group study involved 60 atopic patients randomly allocated, after a 1-week placebo run-in, to once-daily 10 mg Mizolastine (n= 29) or placebo (n= 31) groups. Treatment continued for 8 weeks. Prick tests were performed in duplicate with histamine chlorhydrate (10mg/ml), codeine phosphate (9%), and five increasing concentrations (1–500 reactivity index/ml) of standardized allergen extracts (grass pollen or mites) at days 0, 7, 28, 42, and 56. After 7 days of treatment, inhibition of histamine-induced wheal was -76% and + 20%, respectively, with Mizolastine and placebo (P= 0.0001), in comparison with baseline; inhibition of flare was - 86% and + 50%, respectively, with Mizolastine and placebo (P = 0.0001). Suppression was maintained to a similar extent throughout the study. Results were consistent between histamine-, codeine-, and allergen-induced tests. Safety was satisfactory in both groups. This study confirms Mizolastine as a potent antihistamine which does not induce subsensitivity when taken for 8 weeks, and which can be safely recommended in allergic conditions.
Pierre Attali - One of the best experts on this subject based on the ideXlab platform.
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comparison of the efficacy safety and onset of action of Mizolastine cetirizine and placebo in the management of seasonal allergic rhinoconjunctivitis
Annals of Allergy Asthma & Immunology, 1999Co-Authors: Alfred Sabbah, Jacques Daele, Alan Grierson Wade, Paul Bensoussen, Pierre AttaliAbstract:Background Mizolastine is a potent and selective H 1 -receptor antagonist with additional anti-allergic properties. Objective The aim of this European multicenter, randomized, double-blind study was to compare the efficacy of Mizolastine 10 mg (n = 122), cetirizine 10 mg (n = 125), and placebo (n = 128) once daily for 28 days in patients with seasonal allergic rhinoconjunctivitis (SAR), with focus on the onset of action. Methods Symptoms were evaluated by the investigator using a total symptom score (TS) and by the patient (first week). Responders (R) were patients with a TS decrease of at least 50%. Safety was assessed according to the spontaneous reporting of adverse events. Results Both Mizolastine and cetirizine were effective in relieving the symptoms of SAR. After 7 days of treatment, the improvement in TS and responder's rate were significantly ( P P = .027) and third ( P = .050) day. Both Mizolastine and cetirizine were well tolerated. Conclusion Mizolastine 10 mg once daily is at least as effective as cetirizine in relieving symptoms of SAR, onset of action is rapid with clinical effect evident within 2 hours.
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efficacy and safety of Mizolastine in seasonal allergic rhinitis
Annals of Allergy Asthma & Immunology, 1996Co-Authors: Francisque Leynadier, J Bousquet, Margarita Murrieta, Pierre AttaliAbstract:Background Mizolastine is a new, nonsedating antihistamine under clinical investigation for treatment of allergic rhinitis and urticaria. Objective The purpose of this study was to determine the optimally active dose of once-daily Mizolastine in seasonal allergic rhinitis. Methods This multicenter, double-blind, parallel study involved 494 patients randomly allocated to Mizolastine (5, 10, or 15 mg) or placebo for 2 weeks. Results Physicians' assessments indicated the superiority of 10 and 15 mg Mizolastine to placebo in reducing total symptom scores (P = .002), nasal scores ( P = .004), and ocular scores (P = .007) at day 7. Patients' diaries showed a significant change from baseline in daily symptom scores as early as day 2 (P = .01) in 10- and 15-mg Mizolastine groups in comparison to placebo, but this was not maintained throughout the study. No additional benefits were demonstrated during the second week of treatment in terms of efficacy. Adverse events were slightly more frequent in the 15-mg Mizolastine group. Conclusion This study confirms Mizolastine is an effective and well tolerated antihistamine in the treatment of seasonal allergic rhinitis; 10 mg is the optimal dose.
M Murrietaaguttes - One of the best experts on this subject based on the ideXlab platform.
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Mizolastine in the treatment of seasonal allergic rhinoconjunctivitis a european clinical experience with 5408 patients managed in daily practice paneos sar study
Allergy, 2001Co-Authors: C Bachert, M Murrietaaguttes, V Vovolis, P Margari, J P SantoniAbstract:Background: Mizolastine, a potent H1 antihistamine with additional antiallergic properties, is marketed for the treatment of allergic rhinoconjunctivitis and urticaria. The objective was to investigate the safety and effectiveness of Mizolastine under conditions of daily practice in patients with seasonal allergic rhinoconjunctivitis (SAR). Methods: In an open multicenter study, Mizolastine 10 mg daily was administered for 14 days during the pollen season. Nasal and ocular symptoms, time to onset of symptom relief, and effect of the drug on diurnal alertness were evaluated. Safety was evaluated on the basis of self-reported adverse events (AE). Results: A total of 5408 patients (36±14 years of age, females=57%) with a history of SAR for 8±9 years were treated for a mean of 17.1±5.0 days. SAR symptoms improved in 93% and decreased by at least 50% in 86% of patients; 78% reported improvement after the first drug intake and 51% from the first hour. Sixty-nine percent considered Mizolastine more effective than other antihistamines taken previously. The incidence of AE was low (3.8%). Conclusions: The high responder rate, the rapid onset of action, and the low incidence of AE observed in this large multicenter study confirm the previously reported beneficial efficacy and safety of Mizolastine in the management of SAR.
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humoral and cellular responses to histamine and pollen allergen in a skin chamber model effect of Mizolastine
Annals of Allergy Asthma & Immunology, 2000Co-Authors: L Michel, M Murrietaaguttes, F Jeanlouis, D Levy, Louis DubertretAbstract:Background Mizolastine is a new non-sedative antihistamine and antiallergic drug proven to be effective and safe in the treatment of allergic rhinitis and urticaria. Objective To quantitatively explore the time course of mediator release and cell recruitment during allergen challenge and the effects of Mizolastine on the event, using the skin chamber model. Methods Twelve pollen-sensitive patients (23 ± 6 years)wereincludedina double-blind crossover study. Patients received 10 mg Mizolastine or placebo once daily in the first 4-day period and, after a 3-week washout period, vice-versa in the crossover period. On day 4 of each period, a non-invasive in vivo skin chamber technique was used to determine the alteration of vascular permeability, mast cell mediator release, the release of soluble intercellular adhesion molecule −1(sI-CAM-1) in skin sites challenged with exogenous histamine or grass pollen allergen extract, over an 8-hour period. Results Challenge with allergen-induced significant mast cell activation, as indicated by the release of histamine, tryptase and LTC 4 , in chamber fluids 2 hours after initiation of the allergic reaction and during the following 6 hours. Both exogenous histamine and allergen induced significant vasodilatation, which was sustained during the 8-hour challenge, as indicated by the accumulation of protein in the chamber fluids. Likewise, both histamine and allergen induced the release of significant amounts of ICAM-1 throughout the 8-hour period. Mizolastine significantly inhibited the histamine- and allergen-induced extravasation (after 2 hours, P = .003; after 8 hours, P = .009; after 2 hours, P = .044; after 8 hours, P = .003 respectively) and the histamine- and allergen-induced—ICAM-1 release (after 2 hours, P = .004; after 8 hours, P = .05; after 2 hours, P = .03 respectively). Conclusion Mizolastine strongly inhibited the local response to histamine in this skin chamber model with, of interest, inhibition of the release of the soluble adhesion-molecule ICAM-1.
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one year treatment of chronic urticaria with Mizolastine efficacy and safety
Journal of The European Academy of Dermatology and Venereology, 2000Co-Authors: G Lorette, F Leynadier, Alberto Giannetti, R S Pereira, M MurrietaaguttesAbstract:Aim To assess the long-term safety and efficacy of the H1-receptor antagonist Mizolastine in the symptomatic treatment of chronic urticaria (CU). Background Mizolastine is a novel second generation antihistamine with additional anti-inflammatory properties which has been shown to be effective in this condition as well as in allergic rhinitis. As the drug is used for chronic treatment, a detailed study of its efficacy and safety over a prolonged period was warranted. Methods This open label multicentre trial recruited 211 patients suffering from CU (67% female; mean age 40 ± 13 years), with ≥ 1 episode/week if untreated. After a 7-day placebo run-in period, patients received Mizolastine (10 or 15 mg) for 12 months. Efficacy was assessed by the patient using daily diary cards and overall condition evaluation at study visits. Clinicians also assessed the same parameters at each visit, and gave a global assessment at study termination. Safety was assessed by monitoring adverse events and laboratory parameters. Cardiac safety was monitored every 4 months using 12-lead ECGs, with particular attention to QT intervals. Results The trial was completed by 127 patients. Mizolastine reduced overall discomfort from the second week of therapy, and reduced itching and the number and size of wheals, as assessed by the patients. The clinician’s assessment of the proportion of patients with > 10 wheals decreased from 42% to 28% after 2 months. Clinical assessment also indicated that itch intensity and angioedema were improved by Mizolastine, and the improvement was sustained throughout the trial. The investigators estimated that 70% of patients benefited from therapy. There were no drug-related serious adverse events during the study. The cardiac repolarization assessed according to the QTc intervals was not modified during prolonged administration. Conclusion Mizolastine improves CU symptoms, and these improvements are sustained over 12 months with no loss of drug sensitivity. No specific side-effects are associated with its long-term use in the current study.
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Mizolastine is effective and well tolerated in long term treatment of perennial allergic rhinoconjunctivitis
Journal of International Medical Research, 1999Co-Authors: G Scadding, Aj Tasman, M Murrietaaguttes, Claus BachertAbstract:Abstract The aim of this study was to determine the long-term efficacy and safety of Mizolastine, a new second-generation antihistamine with European approval, in the treatment of perennial allergic rhinoconjunctivitis. In this study, 141 patients were treated with once-daily Mizolastine 10 mg or 15 mg in a 5-month open-label extension of a 1-month double-blind, placebo-controlled trial, which assessed once-daily Mizolastine 10 mg. Mizolastine significantly reduced the nasal subscore (sneezing, rhinorrhoea, itch; end-baseline +/- SD, -2.5 +/- 6.3), nasal obstruction (-1.2 +/- 2.6) and rhinoscopy scores (-1.3 +/- 2.6), and improved ocular and total nasal scores after 6 months' treatment. Improvement was maintained for the duration of the study with no loss of drug efficacy. Adverse effects were mild with no specific effects associated with prolonged use. These results clearly demonstrate that Mizolastine is effective and well tolerated in the long-term treatment of perennial allergic rhinoconjunctivitis. The significant clinical improvement in nasal blockade may reflect Mizolastine's histamine/5-lipoxygenase dual inhibition.
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rapid and sustained efficacy of Mizolastine 10 mg once daily in seasonal allergic rhinitis
Journal of International Medical Research, 1998Co-Authors: M Stern, M Murrietaaguttes, P Blondinertzbischoff, C Hardwicke, E B M Emmerson, M S JuddAbstract:This 28-day, double-blind, randomized study in 256 patients compared the efficacy and safety of Mizolastine 10 mg daily with placebo in patients with seasonal allergic rhinoconjunctivitis. All four nasal symptoms (itch, rhinorrhoea, sneezing, obstruction) and three ocular symptoms (itch, tears, redness) were rated by investigators using both a 0-3 and a 0-9 rating scale. Compared with the placebo group total, nasal and ocular scores were all significantly lower in the Mizolastine-treated patients at day 14 of the study (P = 0.0002-0.0009, using the 0-9 scale) and relief was maintained throughout the 4-week study duration. Patient diary total scores showed that Mizolastine was effective from the first day of treatment. The 0-9 scale appears to be more sensitive than the 0-3 scale for rating symptoms of seasonal allergic rhinitis.