Twenty-four-hour activity and consistency of activity of levocetirizine and desloratadine in the skin.
OBJECTIVE
Levocetirizine, the active enantiomer of cetirizine, and desloratadine, the active metabolite of loratadine, are two recently introduced anti-H1 agents. We set out to compare their antihistaminic activity in the skin for 24 h in a double-blind, randomized cross-over trial.


METHODS
The skin reaction to histamine administered by prick tests (100 mg ml(-1)) was measured by the surface areas of weals and flares for 24 h [before treatment, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 h after a single dose of levocetirizine (5 mg), desloratadine (5 mg) or placebo] in 18 healthy volunteers (34.8 +/- 9.4 years; 14 women). The areas under the curves (AUC) of the weal and flare areas as a function of time were compared by ANOVA.


RESULTS
A highly significant overall treatment effect (P < 0.0001) was observed and both weals and flares were inhibited. The pairwise comparisons showed that the activity of levocetirizine and desloratadine was significantly superior to that of placebo (P < 0.0001), and the activity of levocetirizine was significantly superior to that of desloratadine (P < 0.0001). 'Total' weal inhibition (> or = 95%) occurred only with levocetirizine. Median values of maximal weal inhibition were 44.2% with placebo, 55.0% with desloratadine and 100% with levocetirizine. The time to maximal weal inhibition was 4 h (median value) for all three study drugs, but scattered over a wider range for desloratadine (3-24 h) than levocetirizine (2-4 h). With desloratadine, five of 18 (28%) subjects reached weal inhibition of at least 70% at between 3 and 10 h, whereas with levocetirizine all subjects [18/18 (100%)] reached this level of weal inhibition at between 1 and 3 h. The median duration of 70% weal inhibition was zero with placebo and desloratadine, and was 21.4 h with levocetirizine (P < 0.0001 between the three study drugs, and P < 0.0001 between the two active drugs). No uncommon adverse events were reported, and no subject withdrew from the study due to an adverse event.


CONCLUSIONS
This study shows that the activity of levocetirizine in suppressing skin reactivity to histamine was clearly superior to that of desloratadine for 24 h after a single dose. In addition, its activity was more consistent and lasted longer.
Purohit
Ashok
A
INSERM U425, Service de Pneumologie, Hôpitaux Universitaires, Strasbourg, France.
Melac
Michel
M
Pauli
Gabrielle
G
Frossard
Nelly
N
D000293:Adolescent; D000328:Adult; D017332:Cetirizine / Q000494:pharmacology* / Q000627:therapeutic use; D002940:Circadian Rhythm; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D017336:Loratadine / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000187:drug effects*; D014581:Urticaria / Q000139:chemically induced / Q000517:prevention & control
D006634:Histamine H1 Antagonists; D017336:Loratadine; C121345:desloratadine; D017332:Cetirizine