Single and short-term dosing effects of levocetirizine on adenosine monophosphate bronchoprovocation in atopic asthma.
OBJECTIVE
Adenosine monophosphate (AMP) acts indirectly via primed airway mast cells to induce bronchial hyper-responsiveness, which in turn correlates with eosinophilic asthmatic inflammation and atopic disease expression. We evaluated single and short-term dosing effects of a modern histamine H1-receptor antagonist, levocetirizine, given at the usual clinically recommended dose, on the primary outcome of AMP bronchoprovocation.


METHODS
Fifteen atopic asthmatics were randomized in double-blind, cross-over fashion to receive for 1 week either levocetirizine 5 mg or placebo. There was a 1-week washout period prior to each randomized treatment. The provocative concentration of AMP producing a 20% fall in FEV1 (PC20) was measured after each washout at baseline and at 4-6 h following the first and last doses of each randomized treatment.


RESULTS
Baseline mean +/- SEM values after washout prior to each randomized treatment comparing levocetirizine vs placebo were not significantly different for prechallenge FEV1 (% predicted) 83 +/- 4 vs 82 +/- 4, or AMP PC20 (mg ml(-1)) 45 +/- 24 vs 45 +/- 22, respectively. Airway calibre as prechallenge FEV1 for levocetirizine vs placebo was not significantly different following the first dose 86 +/- 4 vs 82 +/- 4, or the last dose 85 +/- 4 vs 83 +/- 4, respectively. There were significant improvements (P < 0.05) in AMP PC20 comparing levocetirizine vs placebo following the first dose 123 +/- 73 vs 48 +/- 24, a 1.4 doubling dilution difference (95% CI 0.8, 1.9), and the last dose 127 +/- 74 vs 53 +/- 29, a 1.2 doubling dilution difference (95% CI 0.5, 2.0). AMP PC20 was also improved (P < 0.05) by the first and last doses of levocetirizine but not placebo, vs respective baseline values, with there being no difference in the degree of protection between first and last doses.


CONCLUSIONS
Single and short-term dosing with levocetirizine conferred similar improvements in bronchial hyper-responsiveness to AMP challenge, which was unrelated to prechallenge airway calibre. Further studies are indicated to evaluate the longer-term effects of levocetirizine on asthma exacerbations.
Lee
Daniel K C
DK
Asthma & Allergy Research Group, Department of Clinical Pharmacology, Ninewells Hospital & Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK.
Gray
Robert D
RD
Wilson
Andrew M
AM
Robb
Fiona M
FM
Soutar
Patricia C
PC
Lipworth
Brian J
BJ
D000249:Adenosine Monophosphate; D000328:Adult; D000368:Aged; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy; D001985:Bronchial Provocation Tests; D017332:Cetirizine / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D039563:Histamine H1 Antagonists, Non-Sedating / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged
D039563:Histamine H1 Antagonists, Non-Sedating; D000249:Adenosine Monophosphate; D017332:Cetirizine