Wheal Suppression Research Articles

Lack of Clinical Relevance of Bilastine-Food Interaction in Healthy Volunteers: A Wheal and Flare Study

Introduction: The aim of this study was to compare the pharmacodynamic activity of bilastine administered under fasting and fed conditions in healthy volunteers. Methods: In this randomized, open-label, two-period, crossover study involving 24 healthy subjects, once-daily oral bilastine 20 mg was administered for 4 days under fasting and fed conditions, with a 7-day washout period. Bilastine plasma concentrations were measured for 24 h after the first and fourth doses in each period. Pharmacodynamic activity was assessed by wheal and flare surface inhibition and subjective assessment of itching, after intradermal injection of histamine 5 μg. Results: When administered under fed versus fasting conditions, exposure to bilastine 20 mg decreased (mean maximum plasma concentration and area under the curve from time 0 to 24 h decreased by 34.27% and 32.72% [day 1], respectively, and 33.08% and 28.87% [day 4]). Despite this, the antihistaminic effect of bilastine 20 mg was not altered by food. On day 1, as assessed by wheal and flare surface inhibition, the maximum effect and duration of action of bilastine did not differ to a significant extent between fasting and fed conditions, with only a short 30-min delay in the onset of wheal inhibition. At steady state (day 4), bilastine’s pharmacodynamic effects were not significantly affected under fasting or fed conditions. Conclusion: The pharmacokinetic interaction of bilastine with food does not imply a significant reduction of its peripheral antihistaminic efficacy. Despite a slight delay in onset of action on the first treatment day, the global clinical efficacy of bilastine is not affected by coadministration with food.

Comparative Efficacy of Fexofenadine Versus Levocetrizine Versus Desloratadine via 1% Histamine Wheal Suppression Test

Background Urticaria and allergic dermatoses remains a great challenge to treating dermatologist. Histamine is the major mediator in such disorders. Antihistamines as levocetrizine, fexofenadine and desloratadine are often used to treat such conditions. Ability of antihistamines to suppress the allergic response helps to evaluate the efficacy of the medicine. Objective To compare the efficacy of levocetrizine versus fexofenadine versus desloratadine in suppressing histamine induced wheals in adults. Method One hundred and two healthy adult volunteers completed the study. Subjects were randomized into 3 groups using an envelope method. First group received fexofenadine (N=36), second group received levocetrizine (N =37), and third group received desloratadine (N=29). Pretesting was performed by skin prick test with histamine 1% (positive control) and normal saline (negative control). Wheal size was recorded before and after the treatment (at 0.5, 1, 2, 4 and 24 hours). Result At 30 minutes and 1 hour fexofenadine showed statistically significant wheal suppression than levocetrizine and desloratadine (p=0.0016). However by 2 and 4 hours all three antihistamines; fexofenadine, levocetirizine and desloratadine showed significant suppression of wheal. Whereas at 24 hours desloratadine showed greater wheal suppression than levocetrizine and fexofenadine (p= 0.014). Conclusion The results of the present study showed that fexofenadine presented early onset of action but longer suppression of wheal size was seen with desloratadine as compared to other antihistamines. These potentials could be employed in clinical aspects; depending upon the response needed.

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.

Inhibitory effect of Phlai capsules on skin test responses among allergic rhinitis patients: a randomized, three-way crossover study

BackgroundZingiber cassumunar Roxb., commonly known as Phlai in Thai, has been used as a traditional medicine in Thailand for the treatment of various diseases, including inflammation and chronic airway disease. ObjectiveThe purpose of this study was to assess the antihistaminic effect of Phlai on skin testing. Design, Setting, Participants and InterventionThis was a randomized, open-label, three-way crossover study. Twenty allergic rhinitis (AR) patients were enrolled. In randomized sequence, patients received a single dose of Phlai capsules (100 or 200 mg) or loratadine (10 mg) with a washout period of 1 week between each treatment. Main Outcome MeasuresSkin prick testing for histamine and common aeroallergen (house dust mite) were performed before treatment and after 1, 2, 3, 4, 6, 8, 12 and 24 hours of treatment. The main treatment outcomes were the mean wheal and flare responses to the skin prick test after treatment. ResultsBoth 100 mg and 200 mg Phlai doses suppressed wheal and flare responses to house dust mite allergen, but only 200 mg of Phlai capsules significantly suppressed wheal and flare responses to histamine. Repeated measures analysis of variance showed that loratadine caused more wheal and flare suppression than Phlai capsules in responses to the histamine skin prick test. However, there were no significant differences among the effects of 100 mg Phlai capsules, 200 mg Phlai capsules and loratadine in suppression of wheal and flare induced by the mite skin prick test. Both doses of Phlai were well-tolerated with no adverse events. ConclusionBoth 100 mg (compound D 4 mg) and 200 mg (compound D 8 mg) Phlai capsules, when taken as a single therapeutic dose, inhibited skin reactivity to histamine and mite skin prick tests in AR patients. Trial RegistrationThai clinical trial registry (TCTR20160510001).

Fexofenadine and levocetirizine have equivalent effectiveness for persistent allergic rhinitis

Background: Antihistamines are used to treat allergic rhinitis. Whether better pharmacokinetic and pharmacodynamic properties confer higher clinical effectiveness is not known. Objectives: To compare the effectiveness of original fexofenadine, original levocetirizine, and locally-manufactured fexofenadine for treating persistent allergic rhinitis. Methods: Patients with persistent allergic rhinitis were enrolled during June 2010 to December 2013. Patients were allocated to receive original fexofenadine, original levocetirizine, or locally-manufactured fexofenadine forone week. Daily symptoms were self-assessed. Disease specific quality of life, allergen induced wheal and flare size, peak nasal inspiratory flow, and any adverse events were reported at one week. Results: We enrolled 69 patients. There was no significant difference in reduction of mean total symptom score between original fexofenadine, original levocetirizine, and locally manufactured fexofenadine (mean (95% CI);5.52 (3.98, 7.06), 4.32 (2.43, 6.21), 4.45 (2.51, 6.40)) respectively. Improvement in otolaryngic symptoms (P = 0.51),nonotolaryngic symptoms (P = 0.59), work and study performance (P = 0.42), exertion (P = 0.81), sleep disturbance(P = 0.76), social disturbance (P = 0.16), emotional disturbance (P = 0.66), overall general health (P = 0.55),allergen induced wheal (P = 0.44) and flare suppression (P = 0.90), and peak nasal inspiratory flow (P = 0.85)were not significantly different between the 3 groups. All groups similarly reported minor adverse events. Conclusions: There is no difference in effectiveness between fexofenadine and levocetirizine in treating persistent allergic rhinitis. Locally-manufactured and original fexofenadine similarly improve symptoms, nasal air flow, and quality of life. No major drug-related adverse events were reported. Keywords: allergic rhinitis, H1 antagonists, antihistamines, fexofenadine, levocetirizine, local-manufactured drugs,generic

The reservoir effect of topical steroids in vitiliginous skin: A cross-sectional study.

Prolonged and frequent use of topical steroids may lead to decrease in efficacy as well as many local adverse effects. Stratum corneum has a unique property of reservoir effect. To study the reservoir effect of topical steroids in a steroid-responsive condition which may enable a decrease in the dosing frequency of topical steroids. A cross-sectional study design was used. Patients with at least three vitiliginous patches of more than 2 cm 2 present over the trunk or limbs were included. Exclusion criteria were topical or systemic corticosteroid use within the previous 4 weeks, antihistamine use within the previous 7 days, history of any allergy in the past and immunosuppression. Clobetasol propionate cream was applied on the first vitiliginous area (site A) and fluticasone propionate ointment was applied on the second vitiliginous area (site B). The third vitiliginous area, site C (control site) was left without applying any medication. Histamine-induced wheal suppression test was performed on each site, at the same time of the day, on every consecutive day following steroid application, until the values obtained at sites A and B approached those obtained at site C. SPSS software for Windows, version 16.0 was used for statistical analysis. The mean and standard deviation of the various studied parameters were calculated for various treatment groups and compared using analysis of variance (ANOVA) test. Forty patients were included in the study. The average wheal volumes and average erythema sizes at sites A and B were significantly smaller than the corresponding values at site C for up to 5 days after applying medication (P < 0.001). The presence of a cutaneous reservoir of topical steroid was confirmed based on its suppressive effect on the wheal and flare response to histamine. It is not certain that the concentration that suppresses histamine-induced wheal and flare is sufficient for therapeutic efficacy in vitiligo. The reservoir effect of topical clobetasol propionate and fluticasone propionate persisted for 5 days in vitiliginous skin. Hence, it may be possible to reduce the frequency of topical steroid application in vitiligo.

Formulation and Clinical Evaluation of Triamcinolone Acetonide Niosomes: Effect of Iontophoresis on the Permeation Across Skin

Triamcinolone acetonide niosomes were prepared by thin film hydration technique using surfactants Brij 52, Span 20, cetrimide and cholesterol by 23 factorial design. Niosomes were evaluated for their morphology, vesicle size, in vitro drug release and skin permeation study using human skin. From the factorial design it was found that the cetrimide used in the formulation had greater effect on the entrapment efficiency, in vitro drug release and skin permeability and the particle size was found to be in the range of 50-80 nm. Clinical study was carried out using histamine wheal suppression test for the niosomal formulation and was compared with marketed product on healthy human volunteers with and without iontophoresis. It was found that niosomal formulation with iontophoresis at 15 min has more effect than at 60 min and 120 min when compared to the marketed product. Keywords: Histamine wheal suppression, human volunteers, iontophoresis, niosomes, triamcinolone acetonide.

Comparison of reservoir effect of topical corticosteroids in an experimental animal model by histamine-induced wheal suppression test

Introduction:Topical corticosteroids used in various dermatological diseases are available in different potencies and different formulations. The reservoir effect of different potency corticosteroids in the stratum corneum will help the clinicians to choose an appropriate topical steroid to maximize their efficacy and safety as therapeutic agents.Aims:This study was designed to compare the duration of reservoir of different potency topical corticosteroids experimentally in rabbits using histamine-induced wheal suppression test.Materials and Methods:The study was carried out in albino rabbits (as their skin is similar to humans) using four different concentrations of topical steroids, namely mometasone furoate ointment (0.1%), fluticasone propionate ointment (0.005%), betamethasone valerate cream (0.1%), and hydrocortisone butyrate cream (0.1%). These were applied on the back of rabbit on one side and the vehicle was applied on the other. One hour later, histamine-induced wheal suppression test was performed on both sides and wheal area was measured at 10 min for 7 days. Statistical analysis was done by ANOVA followed by post hoc test.Results:Maximum wheal suppression was seen on day 1 (P<0.001) in all four groups, both at test and at control sites. Interday comparison of mean wheal size by topical steroids showed that the reservoir of mometasone furoate ointment (0.1%) persisted till day 4 in the stratum corneum of the skin. In case of fluticasone propionate ointment (0.005%) and betamethasone valerate cream (0.1%), the reservoir persisted till day 2 and for hydrocortisone butyrate cream (0.1%), the reservoir was present only on day 1.Conclusions:It is concluded that the duration of reservoir depends on the potency of topical steroids. Higher the potency more is the duration of reservoir in stratum corneum and vice versa.

The efficacy of clobetasol propionate with varying dilutions of emollient determined by histamine wheal suppression test

Background:The ability of steroids to reduce the histamine wheal was used to assess the efficacy of topical clobetasol propionate with varying dilutions of emollients.Aim:To determine the wheal-suppressing ability of topical clobetasol with varying dilutions of emollient.Materials and Methods:It was a double-blinded randomized study. Twenty-five volunteers were included in the study. Five syringes of 5 ml were taken and the syringes were loaded with either clobetasol propionate 0.05%, emollient, or clobetasol propionate with emollient in dilutions of 1:1, 1:2, and 1:3. The syringes were coded 1 to 5. Five squares of 3 × 3 cm were marked on the flexor aspect of the forearm of the volunteers. After randomization, half fingertip unit of the cream was applied within each square uniformly. Three hours later histamine prick test was performed by the standard method. The wheal was measured after 15 min and the results were recorded. After decoding, results were statistically analyzed by analysis of variance.Result:The decrease in wheal suppression of steroid with emollient (1:1) was same as topical steroid and the wheal suppression decreased with increasing dilutions of steroid.Conclusion:We conclude that steroids and emollients can be mixed in equal proportion (1:1) and the effect is same as steroid alone and increasing dilution of steroids with emollients was not effective in suppressing the wheal.

Study of reservoir effect of clobetasol propionate cream in an experimental animal model using histamine-induced wheal suppression test

Background:Topical corticosteroids used in various dermatological diseases several times a day led to an increase risk of side effects. By demonstrating a significant reservoir of corticosteroids in the stratum corneum, one can maximize their efficacy and safety as therapeutic agents.Aim:The study was designed to demonstrate a reservoir of topically applied corticosteroid clobetasol propionate cream experimentally in rabbits using histamine-induced wheal suppression test.Materials and Methods:The work was carried out on albino rabbits, as rabbit skin is akin to human skin, using a topical steroid. The topical steroid clobetasol propionate 0.05% cream was applied on the back of rabbit, and after 1-h occlusion histamine-induced wheal suppression test was performed and wheal area measured at 10 min till day 7. Statistical analysis was done by ANOVA followed by “Post Hoc” test.Results:Maximum wheal suppression was seen on day 1 (P < 0.001). Interday comparison of mean wheal size showed no significant difference (P > 0.05) on day 2, 3, and 4 as compared to day 1. Day 5-7 show highly significant difference (P < 0.001) as compared to day 1, thereby suggesting that the reservoir effect of topical clobetasol propionate 0.05% cream persisted till day 4.Conclusions:This work demonstrated that histamine-induced wheal by the topical steroid clobetasol propionate 0.05% cream was suppressed till day 4, indicating that the reservoir of topical corticosteroid persisted till day 4.

Effect of mometasone 0.1% and salicylic acid 5% versus mometasone 0.1% on histamine wheal suppression

Effect of mometasone 0.1% and salicylic acid 5% versus mometasone 0.1% on histamine wheal suppression

Pharmacokinetic-Pharmacodynamic Modelling of the Antihistaminic (H1) Effect of Bilastine

To model the pharmacokinetic and pharmacodynamic relationship of bilastine, a new histamine H(1) receptor antagonist, from single- and multiple-dose studies in healthy adult subjects. The pharmacokinetic model was developed from different single-dose and multiple-dose studies. In the single-dose studies, a total of 183 subjects received oral doses of bilastine 2.5, 5, 10, 20, 50, 100, 120, 160, 200 and 220 mg. In the multiple-dose studies, 127 healthy subjects received bilastine 10, 20, 40, 50, 80, 100, 140 or 200 mg/day as multiple doses during a 4-, 7- or 14-day period. The pharmacokinetic profile of bilastine was investigated using a simultaneous analysis of all concentration-time data by means of nonlinear mixed-effects modelling population pharmacokinetic software NONMEM version 6.1. Plasma concentrations were modelled according to a two-compartment open model with first-order absorption and elimination. For the pharmacodynamic analysis, the inhibitory effect of bilastine (inhibition of histamine-induced wheal and flare) was assessed on a preselected time schedule, and the predicted typical pharmacokinetic profile (based on the pharmacokinetic model previously developed) was used. An indirect response model was developed to describe the pharmacodynamic relationships between flare or wheal areas and bilastine plasma concentrations. Finally, once values of the concentration that produced 50% inhibition (IC(50)) had been estimated for wheal and flare effects, simulations were carried out to predict plasma concentrations for the doses of bilastine 5, 10 and 20 mg at steady state (72-96 hours). A non-compartmental analysis resulted in linear kinetics of bilastine in the dose range studied. Bilastine was characterized by two-compartmental kinetics with a rapid-absorption phase (first-order absorption rate constant = 1.50 h(-1)), plasma peak concentrations were observed at 1 hour following administration and the maximal response was observed at approximately 4 hours or later. Concerning the selected pharmacodynamic model to fit the data (type I indirect response model), this selection is attributable to the presence of inhibitory bilastine plasma concentrations that decrease the input response function, i.e. the production of the skin reaction. This model resulted in the best fit of wheal and flare data. The estimates (with relative standard errors expressed in percentages in parentheses) of the apparent zero-order rate constant for flare or wheal spontaneous appearance (k(in)), the first-order rate constant for flare or wheal disappearance (k(out)) and bilastine IC(50) values were 0.44 ng/mL/h (14.60%), 1.09 h(-1) (15.14%) and 5.15 ng/mL (16.16%), respectively, for wheal inhibition, and 11.10 ng/mL/h (8.48%), 1.03 h(-1) (8.35%) and 1.25 ng/mL (14.56%), respectively, for flare inhibition. The simulation results revealed that bilastine plasma concentrations do not remain over the IC(50) value throughout the inter-dose period for doses of 5 and 10 mg. However, with a dose of 20 mg of bilastine administered every 24 hours, plasma concentrations remained over the IC(50) value during the considered period for the flare effect, and up to 20 hours for the wheal effect. Pharmacokinetic and pharmacodynamic relationships of bilastine were reliably described with the use of an indirect response pharmacodynamic model; this led to an accurate prediction of the pharmacodynamic activity of bilastine.

Hydroxyzine and cetirizine pharmacokinetics and pharmacodynamics after oral and intravenous administration of hydroxyzine to healthy dogs

Pharmacokinetic parameters of hydroxyzine and its active metabolite cetirizine were determined after oral and intravenous administration of 2 mg kg(-1) of hydroxyzine to six healthy dogs. Plasma drug levels were determined with high-pressure liquid chromatography. Pharmacodynamic studies evaluated the suppressive effect on histamine and anticanine IgE-mediated cutaneous wheal formation. Pharmacokinetic and pharmacodynamic correlations were determined with computer modelling. The mean systemic availability of oral hydroxyzine was 72%. Hydroxyzine was rapidly converted to cetirizine regardless of the route of administration. The mean area-under-the-curve was eight and ten times higher for cetirizine than hydroxyzine after intravenous and oral dosing, respectively. After oral administration of hydroxyzine, the mean peak concentration of cetirizine was approximately 2.2 microg mL(-1) and that of hydroxyzine 0.16 microg mL(-1). The terminal half-life for cetirizine varied between 10 and 11 h after intravenous and oral administration of hydroxyzine. A sigmoidal relationship was fit to the data comparing cetirizine plasma concentration to wheal suppression. Maximum inhibition (82% and 69% for histamine and anticanine IgE-mediated skin reactions, respectively) was observed during the first 8 h, which correlated with a plasma concentration of cetirizine greater than 1.5 microg mL(-1). Pharmacological modelling suggested that increasing either hydroxyzine dosages or frequencies of administration would not result in histamine inhibition superior to that obtained with twice daily hydroxyzine at 2 mg kg(-1). In conclusion, there was rapid conversion of hydroxyzine to cetirizine. The reduction of wheal formation appeared almost entirely due to cetirizine. Pharmacodynamic modelling predicted that maximal antihistamine effect would occur with twice daily oral administration of hydroxyzine at 2 mg kg(-1).

Comparative efficacy of levocetirizine, desloratidine and fexofenadine by histamine wheal suppression test

Histamine is the major mediator of allergic reactions. Newer H1 antihistaminics like levocetirizine, fexofenadine, and desloratadine are used in the treatment of seasonal and perennial allergic rhinitis and urticaria. The ability to block the cutaneous response to intradermal histamine is used to evaluate the potential of antihistamines. To compare the potency, onset, and duration of action of the commonly used antihistamines-levocetirizine, fexofenadine, and desloratadine. Thirty volunteers were given three single doses of levocetirizine, fexofenadine and desloratadine at weekly intervals. A pretest was performed by using the intradermal histamine prick test. After administration of the drugs, the intradermal test was repeated at (1/2), 1, 2, 3, 6 and 24 h, and the sizes of the wheal were measured. The mean values were taken and were compared by using Levene's t-test. At 30 min, fexofenadine showed a statistically significant suppression of wheal size compared to levocetirizine and desloratadine. Two and three hours after administration, levocetirizine and fexofenadine showed statistically significant inhibition of wheal size while only levocetirizine had this effect after six hours when compared to desloratadine. Desloratadine showed greater inhibition of wheal size at the end of 24 h when compared to levocetirizine and fexofenadine but this was not statistically significant. Fexofenadine had the earliest onset of action while levocetirizine showed maximum inhibition of wheal response after three and six hours.

Ranitidine (150 mg daily) inhibits wheal, flare, and itching reactions in skin-prick tests

H(1)-receptor antagonists are known to suppress reactions in skin-prick tests (SPTs); however, the effect of H(2)-receptor antagonists, which are widely used in our everyday practice, remains unclear. The aim of this study was to determine the influence of ranitidine on wheal, flare, and itching sensation in SPTs. Twenty-one atopic patients (5 women and 16 men) with an average age of 28.04 years (SD, +/-8.24) were tested with histamine, codeine, negative control solution, and standard allergen extracts. Ranitidine (150 mg daily), loratadine (10 mg daily), or placebo were given to the volunteers for 5 days in a double-blind manner with 14 days of washout period. SPTs were applied to the volar surface of a forearm. There was no difference in wheal, flare, and itching between SPTs performed after placebo and washout period. The analysis revealed a statistically significant suppression of wheal and flare by ranitidine and loratadine (p = 0.013 and <0.00001, respectively, for wheals after allergens solutions tests, Wilcoxon rank-sum test). We found a significant suppression of itching induced by ranitidine (reduction of 26.85%; p = 0.005) and loratadine (29.6%; p = 0.005) as compared with placebo (p = 0.068 versus washout). Our data show a suppressive effect of ranitidine on the wheal, flare, and itching sensation in SPT. Because the sensitivity and specificity of skin testing requires withholding medication that could change the skin reactivity, it seems important to take into account the possible influence of H(2)-receptor antagonists on allergy diagnosis and therapy.

Inhibition of allergen‐induced wheal and flare reactions by levocetirizine and desloratadine

The reproducible and standardized histamine-induced wheal and flare model helps identify the objective effectiveness of antihistamines in humans, as well as their differences in onset and duration of action. Some of the newest antihistamines have already been compared in a head-to-head setting using this model. However, their objective action at inhibiting the allergen-induced wheal and flare response has not been reported yet. The time-response study presented here shows the objective activity of two of the newest generation of antihistamines, levocetirizine and desloratadine, at inhibiting the allergen-induced wheal and flare response in a randomized, cross over, placebo-controlled trial. This model is interesting to the clinical setting since allergic subjects are recruited, and the response to allergen involves mast cell degranulation and release of numerous vasoactive and pro-inflammatory mediators additionally to histamine. In addition, this study reports receptor occupancy for both antihistamines at therapeutic dosage, leading to analysis of potential differences in activity. This study clearly shows the potential anti-inflammatory properties of desloratadine and levocetirizine in their skin activity when allergen is the challenging agent as occurs in the clinical situation. To evaluate the inhibitory activity of the new-generation antihistamines levocetirizine and desloratadine at their therapeutic doses on the allergen-induced wheal and flare reaction at 1.5 h, 4 h, 7 h, 12 h and 24 h postdose, and to measure their plasma and skin concentrations. A double-blind, randomized, cross-over, placebo-controlled study in 18 allergic subjects was carried out. The time-response of the wheal and flare reaction areas under the curve (AUC) were compared by anova. Both antihistamines significantly (P < 0.001) inhibited the allergen-induced wheal and flare reactions compared with placebo. Levocetirizine was significantly more potent than desloratadine. Mean +/- SEM wheal AUC(0-24 h) was 506.4 +/- 81.0 with levocetirizine and 995.5 +/- 81.0 mm(2) h with desloratadine as compared with placebo (1318.5 +/- 361.0 mm(2) h). Flare AUC(0-24 h) was 5927.3 +/- 1686.5 and 15838.2 +/- 1686.5 mm(2) h, respectively [P < 0.001 for both compared with placebo (22508.2 +/- 7437.1 mm(2) h)]. Levocetirizine showed significant inhibition of wheal and flare already at 1.5 h postdose compared with placebo (P <or= 0.001); desloratadine achieved a significant effect only after 4 h. The mean total plasma concentration at 12 h and 24 h after intake was higher for levocetirizine (58.1 +/- 13.4 and 20.0 +/- 8.1 ng ml(-1), respectively) as compared with desloratadine (0.82 +/- 0.24 and 0.45 +/- 0.16 ng ml(-1)). Similarly, higher mean unbound skin concentrations were observed for levocetirizine 24 h after intake (1.80 ng g(-1)) than for desloratadine (0.07 ng g(-1)). This was associated with greater receptor occupancy for levocetirizine (54%) than desloratadine (34%) at 24 h. Levocetirizine suppressed the cutaneous allergic reactions with a higher potency than desloratadine, which correlated with its high receptor occupancy. Receptor occupancy rather than drug affinity or plasma half-life is more representative of antihistamine potency.

Efficacy of fexofenadine versus desloratadine in suppressing histamine-induced wheal and flare

To date, no published articles exist comparing the H1-receptor antagonist activities of fexofenadine and desloratadine using the histamine-induced skin wheal-and-flare model. The aim of this study was to compare the efficacy of fexofenadine versus desloratadine in suppressing histamine-induced skin flares and wheals in adults and adolescents. This was a two-center, randomized, placebo-controlled, complete-crossover study. Subjects were administered either single-dose fexofenadine HCl, 180 mg; desloratadine, 5 mg; or placebo and their response to skin-prick testing with histamine and diluent was recorded at predetermined time intervals. The primary end point was change in size of histamine-induced summation skin flares. Secondary end points included change in skin wheal summation measurements, onset, duration, maximum percent suppression, and time to maximum suppression of flares and wheals. Fexofenadine suppressed skin flares significantly more than desloratadine from 2 to 6 hours, and wheals from 2 to 4 hours, 6 to 9 hours, and 12 hours posttreatment. In addition, fexofenadine suppressed flares more than placebo at all time points from 2 to 24 hours and wheals more than placebo at all time points from 2 to 12 hours posttreatment. Desloratadine suppressed flares significantly more than placebo from 6 to 10 hours and at 12 and 24 hours but suppressed wheals significantly versus placebo only at 10 hours. Fexofenadine had a faster onset of flare suppression than desloratadine (1 hour versus 5 hours) and an equally rapid onset of wheal suppression. Fexofenadine HCl, 180 mg, was superior to desloratadine, 5 mg, in histamine-induced wheal-and-flare suppression, suggesting increased in vivo H1-receptor antagonist potency of fexofenadine versus desloratadine.

The effect of montelukast (10 mg daily) and loratadine (10 mg daily) on wheal, flare and itching reactions in skin prick tests

Antileukotriene agents are widely used for the treatment of allergic conditions including bronchial asthma and allergic rhinitis. The influence of montelukast on skin reactivity has not been clearly evaluated. The aim of this study was to determine the effect of montelukast on wheal, flare and itching in skin prick tests (SPTs). Methods Fifteen atopic patients (5 women and 10 men) with average age 28.04 (SD±8.24) were tested with histamine, codeine, negative control solution and allergen extract (grasses). Montelukast (10 mg), loratadine (10 mg) or placebo were given to the volunteers for 5 days in a double-blind manner, followed by SPT, with 14 days of wash-out period. Results There was no differences in wheal, flare and itching ( p = 0.205 ; 0.086 and 0.069 , respectively, Wilcoxon rank-sum test) between SPT performed after placebo and wash-out period. The analysis revealed a statistically significant suppression of wheal and flare by loratadine ( p < 0.05 for all tested solutions). Pre-treatment with montelukast did not influence wheal size ( p = 0.099 , 0.21 , 0.066 for histamine, codeine and allergens, respectively), but significantly reduced flare ( p = 0.005 ; 0.003 ; 0.02 for histamine, codeine and allergens, respectively). We found a significant suppression of itching produced by montelukast ( p = 0.02 ) and loratadine ( p = 0.03 ) as compared to placebo ( p = 0.068 vs. wash out). Conclusions Our data show a tendency to suppressive effect of montelukast on flare and itching but not on wheal which is basic for SPT interpretation. We conclude that found suppression have little impact on clinical effectiveness of SPT as a diagnostic tool.

Study of histamine wheal suppression by dexamethasone with and without iontophoresis

Iontophoresis increases the penetration of drugs into the skin by electric current. The ability of topical steroids to reduce the size of the histamine wheal was used to assess the efficacy of topical dexamethasone delivered with and without iontophoresis. To determine the wheal suppressing ability of dexamethasone delivered with and without iontophoresis. A template with three squares of 3x3 cm was placed on both forearms of 20 volunteers and the edges marked. A gauze piece soaked in 2 ml of dexamethasone solution was placed on the flexor aspect of the left forearm and the electrode, an aluminum foil was placed on it and connected to the negative pole (since dexamethasone is negatively charged). An electric current was passed for 15 minutes. Similarly, on the right forearm, a dexamethasone soaked gauze piece was placed without iontophoresis. Histamine wheal suppression was assessed at the end of 30 min, 1 hr and 2 hrs, on both sides. Statistical analysis was done using an independent t-test. There was a statistically significant difference in wheal suppression at 30 min (p=0.006) on the left hand where iontophoresis was used. Our experiment showed that topical dexamethasone with iontophoresis has the maximum effect at the end of 30 minutes and is more effective than dexamethasone without iontophoresis.

Suppression of the histamine-induced wheal and flare response by fexofenadine HCl 60 mg twice daily, loratadine 10 mg once daily and placebo in healthy Japanese volunteers

SummaryBackground: The effects of the selective H1-receptor antagonist fexofenadine have been widely demonstrated in Western populations; however, to date, limited data comparing the effects of fexofenadine with other antihistamines have been reported in Japanese subjects.Objective: To investigate the effect of fexofenadine and loratadine on the histamine-induced cutaneous wheal and flare response in healthy Japanese volunteers.Methods: Eighteen healthy male and female Japanese volunteers aged 20-53 years were randomized to receive fexofenadine HCl 60 mg twice daily, loratadine 10 mg once daily or placebo in a 1-day, three-period, double-blind, crossover study. For each treatment, the wheal and flare response to 100 mg/mL histamine was assessed at baseline and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 8, 12 and 24 hours post-dose. Blood samples were taken for pharmacokinetic analysis.Results: Fexofenadine produced significantly greater percentage suppression of the overall wheal response compared with placebo and loratadine (43.1% versus 10.0% and 15.2%, respectively; p < 0.001). Similarly, fexofenadine significantly suppressed the overall flare response compared with placebo and loratadine (43.0% versus 3.5% and -8.9%, respectively; p < 0.01). Loratadine was statistically no different from placebo in terms of both overall wheal and flare suppression. Area under the curve analysis for wheal and flare reduction (0-12 hours post-dose) confirmed these findings. For wheal inhibition, fexofenadine had a significantly faster onset of action (defined as time to ≥ 35% inhibition) compared with placebo (p < 0.001) and loratadine (p < 0.01); for flare, fexofenadine had a significantly faster onset of action than loratadine (p < 0.01). Mean maximum inhibition (the mean of the greatest inhibition achieved from baseline for each treatment) for wheal was achieved significantly faster with fexofenadine than loratadine (p < 0.01), and fexofenadine had a significantly longer duration of effect on suppressing wheal and flare compared with placebo and loratadine (p < 0.05 for all). The antihistamine effects of fexofenadine correlated significantly with its Cmax, while loratadine activity did not correlate significantly with its plasma levels.Conclusions: Fexofenadine is a potent suppressor of the histamine-induced wheal and flare response in healthy Japanese volunteers. These results support findings in Caucasian subjects, and confirm that fexofenadine has greater antihistaminergic activity than loratadine in this human model