Comparative in vivo bioactivity of modern H1-antihistamines on AMP challenge in atopic asthma.
BACKGROUND
Modern H(1)-antihistamines differ in their in vitro binding affinity, but their comparative in vivo bioactivity in asthmatic airways is unknown.


OBJECTIVE
We compared clinically recommended doses of 3 H(1)-antihistamines on airway hyperresponsiveness to AMP challenge (the primary outcome variable).


METHODS
Sixteen atopic patients with mild-to-moderate asthma of whom 10 were receiving inhaled corticosteroid therapy (all had positive results to house dust mite on skin prick testing) were randomized in a double-blind, placebo-controlled, cross-over fashion to receive single doses of 5 mg of desloratadine, 180 mg of fexofenadine hydrochloride (FEX), 5 mg of levocetirizine dihydrochloride (LEV), or placebo, with AMP challenge performed 12 hours after dosing.


RESULTS
All H(1)-antihistamines demonstrated significantly greater (P <.05) geometric mean +/- SEM AMP PC(20) values compared with that of placebo (86 +/- 29 mg/mL): desloratadine, 189 +/- 54 mg/mL; FEX, 176 +/- 57 mg/mL; and LEV, 163 +/- 48 mg/mL. Prechallenge forced expiratory flow at 25% to 75% of maximal lung volume (percent predicted) but not FEV(1) was significantly higher (P <.05) for all H(1)-antihistamines compared with that of placebo (53% +/- 4%): desloratadine, 62% +/- 4%; FEX, 62% +/- 4%; and LEV, 59% +/- 3%. There were no significant differences in either AMP PC(20) or lung function values among the H(1)-antihistamines.


CONCLUSIONS
Single doses of H(1)-antihistamines improved airway hyperresponsiveness and small-airways caliber to a similar degree. Data for in vitro binding affinity do not therefore translate into commensurate differences in in vivo bioactivity at clinically recommended doses.
Lee
Daniel K C
DK
Asthma and Allergy Research Group, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK.
Bates
Caroline E
CE
Currie
Graeme P
GP
Lipworth
Brian J
BJ
D000085:Acetates / Q000627:therapeutic use; D000249:Adenosine Monophosphate; D000328:Adult; D000368:Aged; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D017332:Cetirizine; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D006801:Humans; D017336:Loratadine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use; D012130:Respiratory Hypersensitivity / Q000188:drug therapy / Q000503:physiopathology; D016593:Terfenadine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000085:Acetates; D006634:Histamine H1 Antagonists; D010879:Piperazines; D000249:Adenosine Monophosphate; C472067:levocetirizine; D017336:Loratadine; D016593:Terfenadine; C093230:fexofenadine; C121345:desloratadine; D017332:Cetirizine