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

Background: New H-1-antagonists have become available, but there has been n o comparison of their potency for inhibiting histamine in the skin. Methods: Cetirizine 10 mg, ebastine 10 mg, epinastine 20 mg, fexofenadine 6 0 mg, terfenadine 60 mg, loratadine 10 mg, or placebo was given to 14 healt hy male volunteers in a double-blind, crossover randomized manner. Inhibiti on 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, In, 12, and 24 h a fter 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 m etabolite fexofenadine. Loratadine was the least potent inhibitor. Inhibiti on of the flare response paralleled the patterns seen for wheals. The rank order for area under the curve (0-24 h) was cetirizine, epinastine, terfena dine, 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 tr eating allergic disorders.