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

AIM 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. METHODS 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. RESULTS 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 <= 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. CONCLUSIONS Levocetirizine suppressed the cutaneous allergic reactions with a higher potency than desloratadine, which correlated with its high receptor occupancy. Receptor occupancy rather than dry properties of desloratadine and levocetirizine in their skin activity wrug affinity or plasma half-life is more representative of antihistamine potency.