Inhibition of the histamine wheal by ebastine compared with cetirizine, fexofenadine and loratadine at steady state.
The objective of this double-blind, randomized, placebo-controlled, 5-way crossover study was to compare the pharmacodynamic effects of the H1 antihistamine ebastine (10 mg once daily, E10) with those of cetirizine (10 mg once daily, C10), loratadine (10 mg once daily, L10), fexofenadine (60 mg, twice daily, F60 x 2) and placebo (P) after 6 days of treatment in healthy volunteers. The pharmacodynamic variable was the mean percent reduction from baseline (pretreatment) of the wheal area induced by intradermal histamine 0.1% on the morning after 6 days' treatment. A secondary variable was the concentration of histamine required to produce a wheal of area 150 mm2. E10 reduced wheal size more than did P (p < 0.001) or F60 x 2 (p < 0.019). No significant differences were found among E10, C10 and L10. After E10, a significantly greater concentration of histamine was needed to induce a wheal of 150 mm2 than after P (p < 0.001), L10 (p < 0.001) or F60 x 2 (p < 0.001). No significant differences were found between E10 and C10. In conclusion, this study shows that, at the end of the conventional dosing interval, ebastine 10 mg and cetirizine 10 mg once daily in repeated doses suppressed the histamine wheal more effectively than did loratadine 10 mg once daily or fexofenadine 60 mg twice daily.
Carey
W
W
Hammersmith Medicines Research, Central Middlesex Hospital, London NW10 7NS, United Kingdom. wcarey@hmrlondon.com
Warrington
S
S
Boyce
M
M
Luria
X
X
D000293:Adolescent; D000328:Adult; D002090:Butyrophenones / Q000494:pharmacology*; D017332:Cetirizine / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006632:Histamine; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000188:drug therapy*; D007271:Injections, Intradermal; D017336:Loratadine / Q000494:pharmacology*; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D012882:Skin Tests; D016593:Terfenadine / Q000031:analogs & derivatives* / Q000494:pharmacology*
D002090:Butyrophenones; D006634:Histamine H1 Antagonists; D010880:Piperidines; D017336:Loratadine; D016593:Terfenadine; D006632:Histamine; C093230:fexofenadine; C058249:ebastine; D017332:Cetirizine