Comparison of the effect of loratadine on the airway and skin responses to histamine, methacholine, and allergen in subjects with asthma.
Loratadine is a highly selective, long-acting, H1-receptor antagonist. In a randomized, double-blind, crossover study, we evaluated the effects of loratadine, 10 and 20 mg, and placebo administered once daily for 3 days on the skin-wheal responses to histamine, the airway responses to inhaled histamine and methacholine, and the skin-wheal and airway responses to allergen in 12 subjects with asthma. There was no evidence of a bronchodilator action 3 hours after a third oral dose. In the airways, the geometric mean of the provocative concentration of histamine causing a 20% fall in FEV1 after placebo or loratadine, 10 and 20 mg, was 0.68 mg/ml, 2.71 mg/ml (p, not significant), and 5.96 mg/ml (p less than 0.05), respectively. The concentration ratios (value after active treatment/value after placebo) for loratadine, 10 and 20 mg, were 5.1 (p less than 0.05) and 13.4 (p less than 0.05). Neither dose of loratadine had any significant effect on the methacholine dose-response relationship. In the skin, loratadine also displaced the histamine log-concentration response curves to the right with concentration ratios of 4.7 and 6.7, respectively. Loratadine, 10 and 20 mg, had no protective effect on the early or late-phase bronchoconstrictor responses to inhaled allergen. In the skin, loratadine, 20 mg, significantly inhibited the mean wheal area to allergen. Thus, in the dose regimens studied, although loratadine is a moderately potent and selective H1 antagonist in the skin and airways, it failed to attenuate the early and late airway responses to inhaled allergen.
Town
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Immunopharmacology Group, University of Southampton, England.
Holgate
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D000328:Adult; D000485:Allergens / Q000276:immunology; D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D003533:Cyproheptadine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006632:Histamine / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D006801:Humans; D017336:Loratadine; D016210:Methacholine Chloride / Q000494:pharmacology; D008875:Middle Aged; D012867:Skin / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D012882:Skin Tests
D000485:Allergens; D006633:Histamine Antagonists; D016210:Methacholine Chloride; D003533:Cyproheptadine; D017336:Loratadine; D006632:Histamine