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, H-1-receptor agonist. 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 airway, the geometric mean of the provocative concentration of histamine causing a 20% fall in FEV, 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 < 0.05), respectively. The concentration ratios (value after active treatment/value after placebo) for loratadine, 10 and 20 mg, were 5.1 (p < 0.05) and 13.4 (p < 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 7.6, 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 H-1 antagonist in the skin and airways, it failed to attenuate the early and late airway responses to inhaled allergen.