Suppression of the early and late cutaneous allergic responses using fexofenadine and montelukast.
BACKGROUND
The relative contribution of histamine and the cysteinyl leukotrienes to the early and late cutaneous allergic responses (ECAR and LCAR) can be studied using antagonists of these mediators.


OBJECTIVE
To determine the relative suppression of the ECARs and LCARs using standard doses of an H1-receptor antagonist, a cysteinyl leukotriene1-receptor antagonist, and the two antagonists administered concurrently.


METHODS
We carried out a prospective, randomized, double-blind, placebo-controlled, four-way crossover study in 12 highly allergic participants. Intradermal tests with standardized allergen, and with histamine phosphate, LTD4, and saline controls were performed on 5 different test days as follows: pretreatment baseline and at steady state immediately after the seventh and last dose of a 1-week course of treatment with once-daily fexofenadine, 120 mg; montelukast, 10 mg; fexofenadine and montelukast administered concurrently; or placebo. On each test day, the skin test results were read at intervals from 0.25 to 24 hours after the intradermal injections were performed.


RESULTS
After allergen injection, compared with baseline, all treatment regimens significantly decreased the ECAR and LCAR. After allergen injection, compared with placebo, fexofenadine significantly decreased the ECAR and the LCAR from 0.25 to 2 hours and at 8 hours. Montelukast did not significantly decrease the ECAR or LCAR. Fexofenadine and montelukast administered concurrently were not more effective than fexofenadine alone at any time. In the control skin tests, compared with placebo, fexofenadine, but not montelukast, significantly decreased the histamine-induced response, and montelukast, but not fexofenadine, significantly decreased the LTD4-induced response.


CONCLUSIONS
Fexofenadine and montelukast administered concurrently were not significantly more effective than fexofenadine alone in decreasing the ECAR and LCAR. Montelukast does not need to be discontinued before allergen skin testing. Further studies of the effect of concurrent treatment with higher doses of a histamine antagonist and a leukotriene modifier on the allergic response in the skin are needed.
Simons
F E
FE
Health Sciences Clinical Research Centre, Faculty of Medicine, University of Manitoba, Winnipeg, Canada. simons@ms.umanitoba.ca
Johnston
L
L
Gu
X
X
Simons
K J
KJ
D000085:Acetates / Q000009:adverse effects* / Q000627:therapeutic use; D000328:Adult; D000485:Allergens / Q000008:administration & dosage; D003521:Cyclopropanes; D003864:Depression, Chemical; D017449:Dermatitis, Allergic Contact / Q000188:drug therapy* / Q000209:etiology*; D004359:Drug Therapy, Combination; D005260:Female; D006632:Histamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007267:Injections; D017998:Leukotriene D4 / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011804:Quinolines / Q000009:adverse effects* / Q000627:therapeutic use; D013440:Sulfides; D016593:Terfenadine / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors
D000085:Acetates; D000485:Allergens; D003521:Cyclopropanes; D011804:Quinolines; D013440:Sulfides; D017998:Leukotriene D4; D016593:Terfenadine; D006632:Histamine; C093230:fexofenadine; C093875:montelukast; C027556:histamine phosphate