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.
Grant
J A
JA
University of Texas Medical Branch, Galveston 77555-0762, USA.
Danielson
L
L
Rihoux
J P
JP
DeVos
C
C
D000328:Adult; D002090:Butyrophenones / Q000627:therapeutic use; D017332:Cetirizine / Q000627:therapeutic use; D018592:Cross-Over Studies; D003984:Dibenzazepines / Q000627:therapeutic use; D004311:Double-Blind Method; D006632:Histamine / Q000008:administration & dosage; D006634:Histamine H1 Antagonists / Q000008:administration & dosage* / Q000627:therapeutic use*; D006636:Histamine Release; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000188:drug therapy*; D007093:Imidazoles / Q000627:therapeutic use; D017336:Loratadine / Q000627:therapeutic use; D008297:Male; D010880:Piperidines / Q000627:therapeutic use; D012882:Skin Tests; D016593:Terfenadine / Q000031:analogs & derivatives / Q000627:therapeutic use; D014581:Urticaria / Q000188:drug therapy
D002090:Butyrophenones; D003984:Dibenzazepines; D006634:Histamine H1 Antagonists; D007093:Imidazoles; D010880:Piperidines; D017336:Loratadine; D016593:Terfenadine; D006632:Histamine; C093230:fexofenadine; C053090:epinastine; C058249:ebastine; D017332:Cetirizine