A Double-blind, Single-dose, Crossover Comparison of Cetirizine, Ebastine, Epinastine, Fexofenadine, Terfenadine, and Loratadine Versus Placebo: Suppression of Histamine-induced Wheal and Flare Response for 24 H in Healthy Male Subjects

Background: New H1-antagonists have become available, but there has been no comparison of their potency for inhibiting histamine in the skin.

Methods: Cetirizine 10 mg, ebastine 10 mg, epinastine 20 mg, fexofenadine 60 mg, terfenadine 60 mg, loratadine 10 mg, or placebo was given to 14 healthy male volunteers in a double-blind, crossover randomized manner. Inhibition of the wheal and flare response to epicutaneous histamine phosphate (100 mg/ml) challenge was measured at 0, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 h after doses.

Results: Epinastine inhibited the wheal and flare after 30 min. Cetirizine commenced acting at 1 h and was superior to other treatments. Ebastine was no better than placebo until 4 h, but was efficacious thereafter until 24 h. Terfenadine induced potent inhibition after 1 h and was superior to its metabolite fexofenadine. Loratadine was the least potent inhibitor. Inhibition of the flare response paralleled the patterns seen for wheals. The rank order for area under the curve (0-24 h) was cetirizine, epinastine, terfenadine, ebastine, fexofenadine, loratadine, and placebo.

Conclusions: The inhibition of histamine effects in the skin may be useful in predicting the clinical utility of newly introduced antihistamines in treating allergic disorders.