Effects of cetirizine and epinastine on the skin response to histamine iontophoresis

Epinastine and cetirizine are second-generation, nonsedating and long-lasting antihistamines that are now frequently used for the allergic disorders. We have examined the inhibitory effects of these two drugs on the histamine-induced flare and wheal responses using iontophoresis at 1, 2, 4, 8 and 24 h after the oral administration by a double-blind, cross-over and placebo-controlled study. Both cetirizine and epinastine significantly inhibited the histamine-induced flare and wheal responses at 2 h after the oral administration when compared with placebo. The inhibitory effects of cetirizine and epinastine on the flare response lasted long until at 24 h, however, epinastine was less potent than cetirizine. The inhibitory effects on the wheal response was also clearly and significantly evident at 2-8 h by cetirizine and epinastine. At 24 h cetirizine only showed the significant inhibition on the histamine-induced wheal response. In contrast, epinastine seemed to exhibit the inhibitory capacity earlier than did cetirizine. The inhibitory action of the drugs on the histamine-induced wheal response peaked at 4 h after the oral administration. The histamine-induced itch sensation was also markedly or completely suppressed at 2-8 h by the drugs. Thus, both drugs exhibited the potent and long-lasting antihistamine activity on the skin responses induced by histamine iontophoresis.     

Suppression of wheal and flare in histamine test by the main H1 antihistamines commercialized in Brazil

Background:Several dermatoses are mediated by histamine, such as urticaria, angioedema, and papular urticaria. There are no Brazilian studies comparing the potency of antihistamines.Objectives:To evaluate the tolerability and efficacy of the main commercial brand and generic H1 antihistamines, regarding the suppression of the wheal and flare to the histamine test.Methods:A quasi-experimental, open study with 10 healthy adults submitted to the histamine test on the ventral aspect of the forearms. After 20 minutes, wheal and flares were measured. The tests were performed after two hours of intake of dexchlorpheniramine, hydroxyzine, levocetirizine, fexofenadine, cetirizine, loratadine, ebastine, desloratadine, epinastine and rupatadine, as well as generics of loratadine, cetirizine and fexofenadine.Results:All antihistamines presented a reduction in the wheal compared to the control (p <0.02), as well as in the flare, except for rupatadine (p = 0.70). In the internal comparison, cetirizine, fexofenadine, epinastine, levocetirizine, dexchlorpheniramine and hydroxyzine were the most potent, with no difference between them (p > 0.1). As for halo, cetirizine, epinastine, hydroxyzine and fexofenadine were the most potent, with no difference between them (p > 0.1). The most common adverse effect was drowsiness, which was more prevalent among first-generation drugs (p < 0.01). Generic loratadine, fexofenadine and cetirizine halos were higher than their controls (p >0.03)..Study limitations:A single-center study evaluating only aspects related to histamine.Conclusions:Brazilian commercial antihistamines presented different profiles of inhibition of wheal and flares in the histamine test, as well as adverse effects. Generic loratadine, fexofenadine and cetirizine presented larger flares than brand drugs.     

Comparison of the potency of antihistamines

ABSTRACT: First- and second-generation antihistamines have proven effective in the management of patients with urticaria and allergic rhinitis; however, the efficacy of first-generation antihistamines has been compromised by undesirable side effects such as sedation, dry mouth, and blurred vision. Second-generation antihistamines, on the other hand, are less sedating and have fewer side effects than first-generation agents. Recently second-generation agents have been compared for their pharmacologic activities using an epicutaneous histamine-induced wheal and flare model in normal volunteers. Cetirizine was found to be superior to epinastine, ebastine, fexofenadine, terfenadine, loratadine, and placebo in inhibiting the wheal and flare response. Epinastine had the fastest onset of action at 30 minutes and terfenadine proved to be superior to its metabolite fexofenadine.     

Rapid effects of olopatadine hydrochloride on the histamine-induced skin responses

Olopatadine hydrochloride is one of the second-generation nonsedating antihistamines that are used for treating allergic disorders such as urticaria, rhinitis, and atopic dermatitis. We examined the inhibitory effects of this drug on the flare and wheal responses induced by histamine iontophoresis at 30, 60, and 90 min after oral administration in a double-blind, cross-over, and placebo-controlled study. Olopatadine hydrochloride significantly inhibited the histamine-induced flare and wheal responses as early as 60 min after oral administration when compared with placebo. Significant inihibitory effects of olopatadine hydrochloride on the itch responses were seen at 90 min after administration. Thus, olopatadine hydrochloride exhibited a very rapid and potent antihistamine effect on the histamine-induced skin responses.     

Quantitative time course study of the skin response to histamine and the effect of H1 blockers. A 3-week crossover double-blind comparative trial of cetirizine and terfenadine

A controlled, randomized, double-blind, crossover study was performed in 10 healthy volunteers to compare changes of cutaneous blood flow values (CBFV) determined by laser Doppler flowmetry before and after intake of a capsule containing either 10 mg cetirizine or 60 mg terfenadine. After the determination of the initial response to the anti-H1 agents, drugs were taken daily (cetirizine 10 mg, terfenadine 120 mg) over a 3-week period and the cutaneous response to histamine and saline was evaluated weekly, exactly 4 h after the last drug intake. The following significant variations were observed (analysis of variance for repeated measurements, p less than 0.05): (1) there is a decrease of histamine-induced wheal and flare under antihistamines (anti-H1), cetirizine being more potent than terfenadine; (2) CBFV, measured on the usual flare area, i.e. at 1 cm of the site of agonist injection, decreased after drug intake. There was a gradual increase of the CBFV inhibition over the 3-week follow-up, cetirizine being more effective than terfenadine, and (3) at the site of agonist injection, reduction of the edematous wheal was associated with significant increases of CBFV after drug intake. This quantitative pharmacologic in vivo assay on the agonist action indicates that at lower doses, cetirizine has a significantly higher anti-H1 activity than terfenadine and that this effect is maintained over a 3-week period. There was no tachyphylaxis.     

Effects of loratadine and cetirizine on serum levels of neuropeptides in patients with chronic urticaria

H1‐receptor inhibiting drugs, namely loratadine and cetirizine, were frequently used in treatment of chronic urticaria. Urticarial weal and flare reactions, a neurogenic reflex due to neuropeptides, were reported to be more effectively inhibited by cetirizine than loratadine. The aim of this study was to determine and compare the effects of systemic loratadine and cetirizine treatments on serum levels of selected neuropeptides in chronic urticaria. Treatment groups of either systemic loratadine or cetirizine (10 mg/d), consisting of 16 and 22 patients, respectively, were included. Serum levels of stem cell factor (SCF), neuropeptide Y (NPY), calcitonin gene‐related peptide (CGRP), nerve growth factor (NGF), vasoactive intestinal peptide (VIP), and substance P (SP) were detected before and after one week of treatment with antihistamines. Serum NPY and VIP levels were significantly decreased when compared before and after treatment with antihistamines (P < 0.001 and P < 0.01, respectively). SCF and NGF values were also decreased after antihistamine treatment (P < 0.05). Post‐treatment levels of CGRP were significantly higher compared with pretreatment values, while no significant difference was detected between pre and post treatment levels of SP. Cetirizine was significantly more effective than loratadine on lowering serum levels of SCF among the other neuropeptides. Systemic loratadine and cetirizine treatments in patients with chronic urticaria precisely caused variations in serum levels of neuropeptides. The predominant effect of cetirizine compared to loratadine on reducing serum SCF levels might be explained with anti‐inflammatory properties of cetirizine.     

Inhibitory effects of oral prednisolone and fexofenadine on skin responses by prick tests with histamine and compound 48/80

The prick test is a useful skin test for diagnosing immediate hypersensitivity response. Sometimes it is necessary to perform prick tests on patients who have already received antihistamines or corticosteroids. It is, however, occasionally uncertain whether the results of prick tests are reliable. In this study, the inhibitory effects of prednisolone (10 mg/day) and fexofenadine (120 mg/day) on the response to prick tests induced with histamine and compound 48/80 were examined. During a 7-day-continual drug administration, prick tests were performed 8 h after drug administration. The inhibitory effects of fexofenadine on both the histamine- and compound 48/80-induced skin responses were exhibited on the 1st day and persisted from 24 to 36 h after the final administration. The histamine-induced wheal responses were not inhibited by prednisolone, while the compound 48/80-induced flare and wheal responses were significantly inhibited on the 5th day of drug administration. These responses returned to the baseline level 24 h after the last drug administration. Thus, the results of skin tests performed during administration of antihistamines and corticosteroids should be carefully interpreted.     

The effects of astemizole, cetirizine and loratadine on the time course of weal and flare reactions to histamine, codeine and antigen

An open cross-over study was performed to assess the effects of astemizole, cetirizine and loratadine on weal and flare reactions to intradermal histamine, codeine and house dust mite antigen. Percentage inhibition of weal area, flare area and weal volume was greatest for cetirizine, then astemizole and smallest for loratadine. Wealing due to mast-cell degranulation with either codeine or antigen was less inhibited by all three antihistamines than that due to histamine itself. Time-course studies revealed similarities between wealing provoked by codeine and histamine but different characteristics to that induced by antigen.     

Effects of single therapeutic doses of promethazine, fexofenadine and olopatadine on psychomotor function and histamine-induced wheal- and flare-responses: a randomized double-blind, placebo-controlled study in healthy volunteers

Since most first-generation antihistamines have undesirable sedative effects on the central nervous systems (CNS), newer (second-generation) antihistamines have been developed to improve patients’ quality of life. However, there are few reports that directly compare the antihistaminic efficacy and impairment of psychomotor functions. We designed a double-blind, placebo controlled, crossover study to concurrently compare the clinical effectiveness of promethazine, a first-generation antihistamine, and fexofenadine and olopatadine, second-generation antihistamines, by measuring their potency as peripheral inhibitors of histamine-induced wheal and flare. Further, we investigated their sedative effects on the CNS using a battery of psychomotor tests. When single therapeutic doses of fexofenadine (60 mg), olopatadine (5 mg) and promethazine (25 mg) were given in a double-blind manner to 24 healthy volunteers, all antihistamines produced a significant reduction in the wheal and flare responses induced by histamine. In the comparison among antihistamines, olopatadine showed a rapid inhibitory effect compared with fexofenadine and promethazine, and had a potent effect compared with promethazine. In a battery of psychomotor assessments using critical flicker fusion, choice reaction time, compensatory tracking, rapid visual information processing and a line analogue rating scale as a subjective assessment of sedation, promethazine significantly impaired psychomotor function. Fexofenadine and olopatadine had no significant effect in any of the psychomotor tests. Promethazine, fexofenadine and olopatadine did not affect behavioral activity, as measured by wrist actigraphy. These results suggest that olopatadine at a therapeutic dose has greater antihistaminergic activity than promethazine, and olopatadine and fexofenadine did not cause cognitive or psychomotor impairment.     

Double-blind, crossover comparison of olopatadine and cetirizine versus placebo: suppressive effects on skin response to histamine iontophoresis

Olopathadine, a newly developed histamine H1-receptor antagonist, was compared with cetirizine in its suppressive effects on histamine-induced wheal and flare reaction using an iontophoresis technique in a double-blind, crossover, placebo-controlled fashion. As a result, olopathadine was found to have effects comparable to cetirizine. This finding may predict the efficacy of this new H1-antagonist in treating pruritic skin diseases.     

Treatment of Urticaria

Urticaria is a cutaneous syndrome characterized by dermal edema (wheal) and erythema (flare) that blanches with pressure. The lesions typically last less than 24 hours and are usually pruritic. In 1983, Christensen and Maibach summarized the theory behind the use of histamine H₁ receptor antagonists (antihistamines) in clinical dermatology. These agents remain the mainstay of treatment for urticaria. This article reviews the medical literature on the effectiveness of antihistamines in urticarial syndromes, including acute, chronic idiopathic and the physical urticarias. Older antihistamines, such as chlorpheniramine and hydroxyzine, are effective in the treatment of urticarias, but they also have marked sedative and anticholinergic effects. Newer nonsedating antihistamines (second-generation antihistamines) have been developed that have reduced adverse effects because they do not cross the blood-brain barrier; these agents (acrivastine, cetirizine, loratadine, mizolastine, fexofenadine, ebastine, azelastine and epinastine) cause significantly less sedation and psychomotor impairment than their older counterparts. A review of the literature reveals that there are few studies which document the efficacy of second-generation antihistamines in the treatment of acute urticaria, a biologic entity that usually resolves within 3 weeks. We did not identify controlled studies that suggested superiority of any antihistamine in the treatment of acute urticaria. Loratadine or cetirizine, and possibly mizolastine, appear to be treatments of choice for chronic idiopathic urticaria. For symptomatic dermatographism, the combination of an antihistamine and an H₂ antagonist, e.g. chlorpheniramine and cimetidine, appears to be effective. Very few studies have been conducted on the use of antihistamines in the treatment of cold, cholinergic, and pressure urticaria. Antihistamines are the mainstay of urticarial therapy. This evidence-based review suggests that there are efficacy differences between newer, nonsedating antihistamines and older agents in some forms of the disorder. Clearly, further well-controlled clinical trials in larger numbers of patients are needed to clarify the role of these agents in the treatment of urticaria.     

Agonist-antagonist interactions in the skin: comparison of effects of loratadine and cetirizine on skin vascular responses to prick tests with histamine and substance P.

The skin vascular responses (weal, flare, blood flow measurements) elicited by intradermal administration by pricking of histamine (HS) and substance P (SP) were evaluated 6 h after a single intake of anti-H1 agents displaying different activity profile on skin tests at currently recommended dosages (loratadine 10 mg, cetirizine 10 mg) as compared to placebo (P). The weal and flare response and the increases of blood flow occurring in the usual flare area after HS and SP were almost completely abolished by cetirizine. Inhibition of HS- and SP-induced weal and flare reactions was less marked after loratadine and blood flow in the expanding flare after HS and SP showed significant fluctuations over time. In view of the present results and of data obtained in previous experiments with intradermal injection of agonists, we hypothesize that mode of administration of agonists significantly influences the size of the residual weal after anti-H1 agents. We demonstrate that SP weals induced by pricking are largely inhibited by a potent H1 blockade which supports the view that this phenomenon, as well as the SP-flare, is due to SP-induced histamine liberation. We also, for the first time, report on fluctuations recorded at the edge of the developing flare with laser Doppler flowmetry early after prick testing with a weak H1 blockade. This opens up new avenues in dynamically testing H1-receptor occupancy in vivo and in situ in human skin.     

Efficacy and safety of antihistamines in allergic skin disorders

Background For patients with urticaria, H₁-antihistamines remain the gold standard medical treatment of choice. They act by blocking H₁ receptors on the vascular endothelial cell surface. Newer, non-sedating antihistamines such as loratadine also act to some extent by blocking the release of histamine from mast cells, basophils and human skin tissue. Efficacy All of the newer antihistamines (loratadine, terfenadine, astemizole and cetirizine) have been shown to have comparable efficacy to the classic sedating antihistamines and to be significantly superior to placebo in terms of symptom improvement. Loratadine has been shown to be at least as effective as the other non-sedating agents and cetirizine. Antihistamines also have a potential benefit in the management of patients with atopic dermatitis. In two studies, loratadine was found to be significantly superior to placebo in the reduction of pruritus. Safety In terms of safety, the newer antihistamines have important differences. Cetirizine, for example, causes dose-related sedation and functional impairment compared to placebo. In contrast, loratadine has no such sedative effects. Terfenadine and astemizole have also been shown to be free of sedative effects, but exceeding the recommended dose of either may increase the risk of a serious cardiac arrhythmia, torsades de pointes. Plasma levels of both terfenadine and astemizole may also be increased as a result of interaction with various drugs. In contrast, loratadine has not been shown to induce ECG changes, even at doses of 40 mg o.d. for 90 days.     

Effects of bepotastine, cetirizine, fexofenadine, and olopatadine on histamine-induced wheal-and flare-response, sedation, and psychomotor performance

Although many antihistamines are now in clinical use, few studies directly compare their pharmacodynamic and sedative activities in humans in vivo. We designed a double-blind, placebo-controlled, crossover study to compare the inhibitory effects of bepotastine, cetirizine, fexofenadine, and olopatadine on histamine-induced flare-and-wheal response. Systemic sedative effects and impaired psychomotor activities by these drugs were also evaluated. Bepotastine (10 mg twice a day), cetirizine (10 mg once a day), fexofenadine (60 mg twice a day), and olopatadine (5 mg twice a day) or placebo was given in a double-blind manner to seven healthy volunteers before histamine challenge by iontophoresis. At 0, 1, 2, 4, 8, 12, and 24 h following the oral administration of these drugs, histamine iontophoresis-induced wheal-and-flare response was measured. Sedative effects by the drugs were also evaluated by a visual analogue scale for subjective sedation, and by word processor test for psychomotor activity. Each volunteer was tested with all of the drugs (including placebo), administered in a random order with a washout period of at least 1 week. Histamine iontophoresis induced marked wheal-and-flare response in all participants. Bepotastine, cetirizine, fexofenadine, and olopatadine yielded significant reduction of histamine-induced wheal-and-flare response compared to placebo (P < 0.01). Among the drugs, olopatadine and cetirizine suppressed most markedly and persistently histamine-induced wheal-and-flare response, while bepotastine and fexofenadine produced a significant, but less persistent suppression. Olopatadine, fexofenadine, and cetirizine showed a significant systemic sedative effect in this order with bepotastine showing the least sedative effect. Moreover, olopatadine affected psychomotor performance most markedly, which was followed by fexofenadine and cetirizine. These results indicate that bepotastine, cetirizine, fexofenadine, and olopatadine inhibit histamine-induced wheal-and-flare response of humans in vivo and induce a variable systemic sedative effect and impaired psychomotor activity. Although olopatadine and cetirizine showed the strongest and most persistent suppression of histamine-induced wheal-and-flare response, olopatadine showed a considerable sedative effect with impaired psychomotor performance.     

Evaluation of the antihistamine effects of olopatadine,cetirizine and fexofenadine during a 24 h period: a double-blind,randomized, crossover,placebo-controlled comparison in skin responses induced by histamine iontophoresis

Potency of the antihistamine effects of olopatadine, cetirizine and fexofenadine in standard-dose application were compared from 11.5 to 24 h after application. The test was designed in a double-blind, randomized, crossover, placebo-controlled study of ten healthy volunteers on histamine-induced flare and wheal response using an iontophoresis technique. The suppressive effect of olopatadine on the wheals induced by a 0.1-mA histamine iontophoresis lasted for 24 h after dosing. Fexofenadine administered using the same regimen was the least effective among three drugs tested. Suppression of the wheal response by cetirizine, taken once-daily, decreased with time. Olopatadine completely suppressed even the wheal response induced by a 0.2-mA histamine iontophoresis, although fexofenadine and cetirizine were less effective on the wheals induced by the same histamine challenge. There were no significant differences in subjective drowsiness and objective cognitive function between drug- and placebo-treated subjects. These results demonstrate that olopatadine is the most potent antihistamine among the three H(1)-blockers when administered in a standard dosage.     

比拉斯汀在荨麻疹治疗中的应用

比拉斯汀是一种新型的H1受体拮抗剂,口服可治疗过敏性鼻炎和荨麻疹,其吸收较快,但食用食物和果汁后吸收减慢.已有数据证实,相比其他受体,比拉斯汀对H1的亲和力更高,并能降低组胺和细胞因子水平.在由组胺引起的皮肤风团和红斑上,比拉斯汀20 mg与西替利嗪10 mg相比具有等同疗效,可能有更快的抑制作用.比拉斯汀无抗胆碱作用,不影响驾驶,除此之外,比拉斯汀还具备良好的耐受性,无镇静作用、心脏毒性和肝脏毒性等优点.     

Topically applied aspirin decreases histamine-induced wheal and flare reactions in normal and SLS-inflamed skin,but does not decrease itch. A randomized,double-blind and placebo-controlled human study

Topically applied aspirin has recently been reported to decrease histamine-induced itch in human volunteers. Our aim is to confirm this and to study the antipruritic ability of topical aspirin in inflamed skin. In 24 non-atopic volunteers, an inflammatory skin reaction was induced in forearm skin at 5 different sites by sodium lauryl sulphate contained in Finn Chambers. Aspirin 10%, aspirin 1%, mepyramine 5% and vehicle were applied to the inflamed and corresponding non-inflamed areas 20 min before itch induction with intradermal histamine injection. Itch and pain were scored on a visual analogue scale at regular intervals. Wheal and flare areas were measured. No difference in itch intensities was found after application of aspirin, mepyramine and vehicle, but more itch was induced in aspirin and mepyramine pretreated sites in inflamed skin compared to normal skin (p<0.05). In normal skin, flare areas were smaller after pretreatment with aspirin 10% (p<0.05) and mepyramine (p<0.001), as were wheal areas after mepyramine (p<0.01), compared to vehicle pretreatments. In inflamed skin, flare areas were smaller after pretreatment with aspirin 10% (p<0.01) and mepyramine (p<0.001), as were wheal areas after aspirin 10% (p<0.01), aspirin 1% (p<0.05) and mepyramine (p<0.001). We conclude that despite a significant skin penetration as measured by the influence on wheal and flare reactions, topically applied aspirin did not decrease histamine-induced itch in the model used.     

Effects of H1 antagonists on the cutaneous vascular response to histamine and bradykinin: a study using scanning laser Doppler imaging

Histamine plays an important part in the cutaneous weal and flare response which underlies many allergic skin conditions. It has a direct effect on the local vasculature to promote vasodilatation and increase microvascular permeability and may also initiate the more widely spread neurogenic flare. Quantification of these responses and studies of the mediator mechanisms underlying them have been limited by the lack of appropriate techniques to investigate them. To address this we have used two relatively new techniques, scanning laser Doppler imaging (LDI) and dermal microdialysis to measure changes in skin blood flow and the release of histamine within the weal and flare, following intradermal injection of histamine or bradykinin. These measurements have been made both in the absence and presence of the H₁ receptor blockers cetirizine and loratadine. Scanning LDI of the inflammatory response revealed marked differences in both the development and steady state responses to the intradermal injection of histamine (1–3 μmol/L) and bradykinin (1 μmol/L). The development of the flare and the weal response to both histamine and bradykinin was significantly reduced by cetirizine but not by loratadine. The histamine-induced flare area fell by 57 ± 4% (mean ± SEM, n = 10, P < 0.001) after cetirizine and the area of the weal fell by 73 ± 11% (P < 0.009). Bradykinin-induced inflammatory responses were similarly reduced by cetirizine, the weal by 60 ± 16% (P < 0.02) and the flare by 61 ± 4% (P < 0.005). Measurement of histamine concentration in skin using microdialysis, in six subjects, confirmed that histamine levels rose in the dialysate collected from the weal to 310 ± 16 nmol/L following injection of histamine. Histamine levels also rose following bradykinin injection in some subjects (mean 147 ± 46 nmol/L, range 18–336). Little increase in histamine concentration was seen in the dialysate from the flare following injection of either histamine or bradykinin. The histamine concentration in dialysate from unprovoked skin was 4.19 ± 0.75 nmol/L. These data reveal differences in the dermal responses to different mediators when assessed using scanning LDI. They confirm that histamine is released within the weal but not the flare response to the intradermal injection of both histamine and bradykinin and that its effects on the local vasculature to cause the oedematous weal and the axon reflex-mediated flare are significantly attenuated by the H₁ antagonist cetirizine and to a lesser extent by the H₁ antagonist loratadine.     

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

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.     

Inflammatory skin responses induced by icatibant injection are mast cell mediated and attenuated by H(1)-antihistamines

Icatibant, a bradykinin-2 receptor antagonist, is administered by subcutaneous injection for the treatment of attacks of type I and type II hereditary angioedema. Following injection, patients feel transient pain followed by a short-lived wheal and flare response at the injection site. We hypothesized that the icatibant-induced wheal and flare response follows histamine release from activated skin mast cells and would therefore be reduced by an H(1)-antihistamine. Intradermal injection of 100 μl of 100 μg/ml histamine and 10 mg/ml icatibant into the forearms of health volunteers caused wheal and flare responses of a similar magnitude which were reduced by cetirizine pretreatment by 49% and 41% (histamine) and 35% and 41% (icatibant). Studies in vitro showed that icatibant at 1 × 10(-4) and 1 × 10(-5) M caused significant (P < 0.05) histamine release from isolated human cutaneous mast cells. In conclusion, icatibant induces histamine-mediated wheal and flare responses that may be reduced in severity by prophylactic administration of an H(1)-antihistamine.