Time-dependent inhibition of histamine-induced cutaneous responses by oral and intramuscular diphenhydramine and oral fexofenadine.
BACKGROUND
Diphenhydramine is often the treatment of choice for acute urticarial or allergic reactions despite its adverse effects of sedation and impairment. Second- and third-generation histamine1-antihistamines are generally devoid of these adverse effects but are typically not used because of a perceived slower onset of action.


OBJECTIVE
To examine the time-dependent effects of oral fexofenadine and oral and intramuscular diphenhydramine to reduce histamine-induced wheal-and-flare responses.


METHODS
Eighteen healthy patients were included in a double-blind, placebo-controlled, 3-way, randomized, crossover study with oral fexofenadine (180 mg) and oral and intramuscular diphenhydramine (50 mg). Histamine-induced skin tests were performed before and more than 6 hours subsequent to dosing. The primary end point was time to induce a 50% reduction in histamine-induced flare. Secondary end points included change from baseline at each time point in wheal-and-flare responses and area under the curve at more than 6 hours for flare.


RESULTS
No significant differences were found in the 50% inhibitory responses of histamine-induced flares among the 3 groups (P = .09). No significant differences were found among the 3 groups in change from baseline at each time point except for 30 minutes during which fexofenadine had no inhibitory effect. Area under the curve analyses for wheal-and-flare responses revealed no differences among treatments at more than 6 hours.


CONCLUSIONS
Diphenhydramine tended to work more rapidly than fexofenadine, but the differences were not statistically significant. Given the adverse effect profile of diphenhydramine, but only marginal onset of action advantage, the risk-to-benefit ratio may be more favorable for oral fexofenadine when treating an acute urticarial or allergic reaction.
Jones
Douglas H
DH
Division of Allergy, Asthma, and Immunology, Creighton University Medical Center, Omaha, Nebraska 68131, USA. dhjones@creighton.edu
Romero
Francisco A
FA
Casale
Thomas B
TB
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D002648:Child; D018592:Cross-Over Studies; D004155:Diphenhydramine / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006632:Histamine / Q000008:administration & dosage / Q000276:immunology; D039563:Histamine H1 Antagonists, Non-Sedating / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D012882:Skin Tests; D016593:Terfenadine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
D039563:Histamine H1 Antagonists, Non-Sedating; D016593:Terfenadine; D006632:Histamine; D004155:Diphenhydramine; C093230:fexofenadine