Effect of cetirizine on histamine- and leukotriene D 4-induced bronchoconstriction in patients with atopic asthma

Abstract

Cetirizine, a derivative of hydroxyzine, is a new compound with potent antihistaminic property without antiserotonin and anticholinergic activities. The effect of both a single dose (15 mg) and 7 days of treatment (15 mg twice daily) with cetirizine, a potent H 1 antagonist on bronchoconstriction induced by histamine and leukotriene D 4 (LTD 4) has been examined in 10 patients with mild atopic asthma in a placebo-controlled, double-blind, crossover study. Cetirizine, after a single dose and 7 days of treatment with placebo, the geometric mean values of the provocative concentration of histamine causing a 20% fall in FEV 1 (millimolars) were 1.60 (95% confidence interval, 0.82 to 3.11) and 1.67 (0.77 to 3.65), compared with 118.07 (77.22 to 180.54) ( p < 0.0001) and 53.16 (20.50 to 137.84) after cetirizine administration ( p < 0.0002). The mean inhibition after a single dose was twofold higher than after 1 week of treatment ( p < 0.05). After a single dose and 7 days of treatment with placebo, the geometric mean values of the provocative concentration of LTD 4 causing a 20% fall in FEV 1 (micromolars) were 2.26 (1.74 to 2.94) and 2.37 (1.77 to 3.17), compared with 3.90 (2.60 to 5.86) ( p < 0.05) and 3.21 (2.28 to 4.52) after cetirizine administration. This result suggests that cetirizine is a potent H 1 antagonist in the human airways. Diminished activity after 1 week of treatment suggests subsensitivity of H 1 receptors developing in human airways. The small protective effect after a single dose against LTD 4-induced bronchoconstriction indicates a nonspecific rather than a specific receptor antagonism.