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

Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• 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. WHAT THIS STUDY ADDS• 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. AIMSTo 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. METHODSA 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. RESULTSBoth antihistamines significantly (P < 0.001) inhibited the allergen-induced wheal and flare reactions compared with placebo. Levocetirizine was significantly more potent than desloratadine. Mean Ϯ SEM wheal AUC(0-24 h) was 506.4 Ϯ 81.0 with levocetirizine and 995.5 Ϯ 81.0 mm 2 h with desloratadine as compared with placebo (1318.5 Ϯ 361.0 mm 2 h). Flare AUC(0-24 h) was 5927.3 Ϯ 1686.5 and 15 838.2 Ϯ 1686.5 mm 2 h, respectively [P < 0.001 for both compared with placebo (22508.2 Ϯ 7437.1 mm 2 h)]. Levocetirizine showed significant inhibition of wheal and flare already at 1.5 h postdose compared with placebo (P Յ 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 Ϯ 13.4 and 20.0 Ϯ 8.1 ng ml -1 , respectively) as compared with desloratadine (0.82 Ϯ 0.24 and 0.45 Ϯ 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. CONCLUSIONSLev...

The effectiveness of levocetirizine and desloratadine in up to 4 times conventional doses in difficult-to-treat urticaria

“…Furthermore, the results strongly suggest that levocetirizine is the more effective of the 2 drugs in relieving whealing and itching, a conclusion supported by a previous 4-week trial in chronic urticaria 17 and wheal and flare studies comparing levocetirizine and desloratadine. [18][19][20][21] A recent study suggested that using higher doses of desloratadine in subjects with cold-induced urticaria had a beneficial effect. 22 This is in line with our results, which were, however, obtained in patients with difficult-to-treat urticaria.…”

Possibilities of Use of the Modern Antihistamine Medicines in Therapy of Patients With Allergic Rhinitis

“…Максимальное уменьшение воспалительных проявлений наблюдалось через 24 ч после приема дезлоратадина (6%) и плацебо (33%) и через 7 ч после приема левоцети-ризина (87%) (рис. 6) [26][27][28][29].…”

Antihistamines in Treatment of Chronic Urticaria. Review of Modern Recommendations

“…Simons изуча-лись концентрации в крови и коже (при биопсии) и пода-вление образования кожных реакций в гистамин-инду- Примечание. Адаптировано по ссылкам [45][46][47][48][49][50][51][52][53][54][55][56].…”