Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042109 (urticaria)
 6,569 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 (10 mg/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 +5%, 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. The 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.
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PMID:Lack of subsensitivity to mizolastine over 8-week treatment. 879 22

A two-centre, double-blind, randomized, placebo (P)-controlled, parallel-group study was conducted in the UK to examine the efficacy and safety of mizolastine (M), a new H1-receptor antagonist, as a once-daily 10-mg dose in chronic idiopathic urticaria. Fifty-six outpatients (M: n = 28; P: n = 28) with a mean age of 38 +/- 15 years, a duration of disease of more than 3 years, and symptoms of urticaria at least twice a week in the absence of treatment were recruited. After a single-blind placebo run-in period, patients were allocated to one of two treatment groups and were evaluated after 7 and 28 days. The main characteristics (age, duration of disease, number of urticarial episodes, and total score) of the two groups were comparable at inclusion. Mizolastine was shown to improve the urticaria symptoms: at the end of the study, mizolastine produced a significantly greater decrease in the global symptom score comprising itch, wheals, and erythema (M: 2.1 +/- 2.1 vs P: 0.4 +/- 2.0; P = 0.002). The patient-rated global discomfort from symptoms measured by visual analog scale was significantly improved with mizolastine (M: 31.4 +/- 36.7) compared to placebo (P: 5.4 +/- 27.6; P = 0.003), with respectively more M responders (74.1%) than P responders (28.6%, P = 0.001), a responder being a patient with a > or = 50% decrease in VAS. Premature dropouts due to lack of efficacy and loss to follow-up mainly occurred at the first evaluation (day 7) and were more often observed in patients in the placebo group (n = 17) than in the mizolastine group (n = 8) (P = 0.031). No serious adverse events were recorded. Somnolence was reported in two mizolastine patients, one of whom discontinued the study. Thus, mizolastine may be considered a new treatment option for the symptoms of chronic urticaria.
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PMID:Efficacy of mizolastine, a new antihistamine, compared with placebo in the treatment of chronic idiopathic urticaria. 883 36

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.
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PMID:Inhibition of histamine-induced skin wheal and flare after 5 days of mizolastine. 893 46

Mizolastine, a new H1-receptor antagonist, is highly selective for histamine H1 receptors and has no anticholinergic, antiadrenergic, or antiserotonin activity. It is rapidly absorbed after oral ingestion, with peak plasma concentrations occurring at 1.5 h. The distribution and terminal elimination half-life values are 2 and 13 h, respectively, in healthy young adult volunteers. Half-life values are longer in the elderly and in subjects with chronic renal insufficiency; however, the differences are not large enough to be clinically relevant or to necessitate a dose adjustment in these populations. Mizolastine produces prompt, sustained, peripheral blockade of histamine H1 receptors in the skin. Suppression of the histamine-induced wheal and flare begins 40-60 min after ingestion of a 10-mg dose, peaks at 3-4 h, lasts for at least 24 h, and does not decrease during regular once-daily dosing. The amount of wheal suppression is comparable to that produced by other leading new H1-receptor antagonists. These pharmacokinetic and pharmacodynamic studies of mizolastine provide its clinical pharmacology 'signature'. They also provide the scientific rationale for recommending a once-daily 10-mg dose and suggest that the efficacy and effectiveness of mizolastine will be widely confirmed in allergic disorders, especially rhinitis and urticaria.
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PMID:Mizolastine: antihistaminic activity from preclinical data to clinical evaluation. 1020 99

Antihistamines (H1-receptor antagonists) are amongst the most frequently prescribed drugs worldwide for the treatment of allergic conditions. The clinical interest of classical 'first generation' antihistamines is currently rather limited by their anticholinergic and sedative properties. The second generation of antihistamines, so-called non-sedating antihistamines, are free of these side-effects. However, since the 1990s, there have been reports that certain non-sedating antihistamines, mainly terfenadine and astemizole, might be associated with the risk of rare but severe dysrhythmias. These drugs prolong the monophasic action potential and surface electrocardiographic QT interval and may lead to the development of early after-depolarization and possibly torsades de pointes through an inhibition of potassium channel repolarization. Concomitant administration with drugs that inhibit the hepatic cytochrome P-450 (imidazole antifungals, macrolide antibiotics) or those that prolong the QT interval by the same or other mechanism (e.g. antiarrhythmics, antipsychotics, tricyclic antidepressants) increases their effect on the cardiac repolarization. The cardiac safety profile of newer non-sedating antihistamines requires confirmation. Drugs with low or no potential to block the K + rectification channel (e.g. IKr channels) are likely to possess cardiac safety advantages. Other drug-related factors such as the physico-chemical properties of the antihistamines and its metabolic profile may also contribute to the cardiac response. Mizolastine is a new non-sedating antihistamine with antiallergic properties. It has a good bioavailability and a metabolism via the cytochrome P-450 oxidation accounting for only 35% of its hepatic clearance. In addition, mizolastine displays low lipophilicity and consequently low cardiac tissue fixation. In clinical studies, mizolastine has not shown any dose-related increase in QT intervals. Its clinical use has not been associated with ventricular dysrhythmias. Thus, although the post-marketing experience with mizolastine is still limited, mizolastine offers a safe alternative for the therapeutic management of allergic rhinitis and urticaria. However, more data are still needed on the cardiac safety of this and other non-sedating antihistamines.
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PMID:The current cardiac safety situation with antihistamines. 1020 1

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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PMID:Comparative therapeutic effect and safety of mizolastine and loratadine in chronic idiopathic urticaria. URTILOR study group. 1072 19

Urticaria is a common disorder that adversely affects quality of life; work-related and recreational activities are restricted, while rest, sleep, and emotions are seriously disturbed in a significant proportion of patients. The pathogenic mechanisms vary, but cutaneous mast-cell activation with release of histamine and other vasoactive or proinflammatory mediators is thought to be the final common pathway for lesion induction in most cases. A subsequent, but incompletely understood, late-phase allergic reaction seems to prolong the inflammatory process, particularly in certain chronic forms of the disorder. Although histamine is considered an important mediator of urticaria, additional substances, including the cysteinyl leukotrienes (LTs), are putative mediators of the immediate urticarial responses and the inflammatory events that follow in some types of urticaria. A second-generation antihistamine, mizolastine, which exhibits dual activity with selective H1-receptor antagonism and, as shown in animal studies, anti-5-lipoxygenase activity, represents an advance in the treatment of urticaria. It has rapid, potent and sustained action. At the recommended 10-mg dose, mizolastine suppresses the histamine-induced wheal reaction as early as 1 h after oral administration. Compared to placebo, mizolastine significantly reduces overall patient discomfort and pruritus in patients with chronic idiopathic urticaria. Double-blind, placebo-controlled studies have also shown mizolastine to be at least as effective as other second-generation antihistamines. Furthermore, with long-term use of mizolastine over 1 year, a reduction in pruritus and the number of urticarial episodes was maintained with no evidence of tachyphylaxis or tolerance. Mizolastine has also been shown to be an effective treatment for cold-induced urticaria, causing significant delay in the whealing response to the ice-cube test and also reducing the wheal diameter.
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PMID:Clinical advantages of dual activity in urticaria. 1129 78

Mizolastine is a new histamine H1 receptor antagonist. Mizolastine 10 mg/day is effective in allergic rhinitis and chronic idiopathic urticaria. In young healthy volunteers, absorption of mizolastine is rapid with time (tmax) to peak concentration (Cmax) of about 1 hour. The absolute bioavailability of mizolastine 10mg tablets is about 65%. Distribution is rapid with a mean distribution half-life of 1.5 to 1.9 hours. Mizolastine is >98% bound to serum albumin and the apparent volume of distribution is between I and 1.4 L/kg. Mizolastine is extensively metabolised by hepatic glucuronidation and sulphation, with no major active metabolite, and excreted in faeces. The terminal elimination half-life (t1/2beta) is 7.3 to 17.1 hours. The apparent oral clearance after a repeated oral dose of 10mg is 6.02 L/h, with steady state reached from day 3 and no accumulation between days 1 and 7. Cmax and area under the concentration-time curve (AUC) are linearly related to dose. Mizolastine appears in vivo to be a relatively weak inhibitor of cytochrome P450 2E1, 2C9, 2D6 and 3A4. In vivo, no interactions were observed between mizolastine and lorazepam or ethanol. A significant increase in Cmax and trough plasma concentration (Cmin) of digoxin occurred after coadministration with mizolastine, without change in AUC, tmax or clinical parameters. Significant increases in theophylline Cmin and AUC were observed after coadministration with mizolastine. Mizolastine Cmax and AUC were increased when coadministered with erythromycin, with no change in t1/2beta. Concomitant administration of mizolastine and ketoconazole increased mizolastine AUC values with no change in t1/2beta. In a population analysis of the pharmacokinetics of mizolastine in patients with allergies, parameter values were close to those in healthy volunteers, except for duration of absorption, which was almost doubled in the patients. Bodyweight and creatinine clearance were found to have little influence on oral clearance, and no influence of liver transaminases was found on clearance and distribution. Pharmacokinetic parameters of mizolastine in elderly individuals were similar to those observed in healthy young volunteers. In patients with chronic renal insufficiency, t1/2beta was prolonged by 47% compared with young healthy volunteers. In patients with cirrhosis, tmax was longer, Cmax was lower, distribution half-life was prolonged and AUC was 50% higher than in healthy volunteers. In pharmacodynamic-pharmacokinetic trials, the percentage of wheal and flare inhibition was found to correlate with mizolastine Cmin values. No direct relationship was found between drug concentrations in skin blister fluid and antihistamine activity.
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PMID:Clinical pharmacokinetics of mizolastine. 1151 Jun 27