Skin concentrations of H1-receptor antagonists.
BACKGROUND
H1-receptor antagonists are widely used in the treatment of allergic skin disorders.


OBJECTIVE
We sought to evaluate the extent of fexofenadine and diphenhydramine distribution into the skin concomitantly with their peripheral H1-receptor antagonist activity.


METHODS
In a prospective, randomized, double-blind, parallel-group study, 7 men received 120 mg of fexofenadine, and 7 received 50 mg of diphenhydramine. Before dosing; at 1, 3, 6, 9, and 24 hours after the first dose; and at 168 hours (steady-state), 12 hours after the seventh and last daily dose, blood samples and skin punch biopsy specimens were obtained, and epicutaneous tests with histamine phosphate, 1 mg/mL, were performed.


RESULTS
Fexofenadine penetrated the skin to a significantly greater extent than diphenhydramine at 6, 9, 24, and 168 hours (P < or = .05). Maximum skin/plasma ratios of both the H1-antagonists (41.3 +/- 7.8 for fexofenadine and 8.1 +/- 4.4 for diphenhydramine) were obtained at 24 hours. Fexofenadine also produced significantly greater suppression of wheals at 3, 6, and 9 hours and of flares at 3, 6, 9, and 168 hours compared with diphenhydramine (P < or = .05).


CONCLUSIONS
In disorders in which the presence and the effects of H1-receptor antagonists in the skin are clinically relevant, our results support the use of fexofenadine and indicate the need to re-examine the role of diphenhydramine.
Department of Pediatrics & Child Health, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
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D000328:Adult; D004155:Diphenhydramine / Q000097:blood / Q000627:therapeutic use; D004311:Double-Blind Method; D006634:Histamine H1 Antagonists / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000188:drug therapy; D008297:Male; D011446:Prospective Studies; D012867:Skin / Q000737:chemistry*; D016593:Terfenadine / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use
D006634:Histamine H1 Antagonists; D016593:Terfenadine; D004155:Diphenhydramine; C093230:fexofenadine