Article date: February 2008
By: Nelly Frossard, Margherita Strolin‐Benedetti, Ashok Purohit, Gabrielle Pauli, in Volume 65, Issue 2, pages 172-179
What is already known about this subject
Aims
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 mm2 h with desloratadine as compared with placebo (1318.5 ± 361.0 mm2 h). Flare AUC(0–24 h) was 5927.3 ± 1686.5 and 15838.2 ± 1686.5 mm2 h, respectively [P < 0.001 for both compared with placebo (22508.2 ± 7437.1 mm2 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 drug affinity or plasma half‐life is more representative of antihistamine potency.
DOI: 10.1111/j.1365-2125.2007.03009.x
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