Am. J. Respir. Crit. Care Med., Volume 163, Number 6, May 2001, 1420-1425

Fexofenadine Decreases Sensitivity to and Montelukast Improves Recovery from Inhaled Mannitol

JOHN D. BRANNAN, SANDRA D. ANDERSON, KERRY GOMES, GREGORY G. KING, H. KIM CHAN, and J. PAUL SEALE

Department of Respiratory Medicine, Royal Prince Alfred Hospital, Camperdown, NSW, Australia; and Institute of Respiratory Medicine, and Departments of Pharmacy and Pharmacology, University of Sydney, Sydney, NSW, Austraila

We studied, separately, the effects of the histamine antagonist, fexofenadine hydrochloride, and the leukotriene antagonist, montelukast sodium, and their placebos on airway sensitivity to and recovery from inhaled mannitol in subjects with asthma. Two 180-mg doses of fexofenadine were taken over 14 h, and three 10-mg doses of montelukast over 36 h, with the last dose 5 h before challenge. Fexofenadine reduced sensitivity to mannitol and the PD₁₅ was (mean [95% confidence interval] 138 [95, 201]) mg versus placebo (51 [25, 106] mg) (p < 0.001). The final percent reduction in FEV₁ with fexofenadine was 20.8 ± 5.4% and not different from placebo (20.1 ± 5.3%) (p = 0.7); however, recovery was slower with fexofenadine compared with placebo (p < 0.001). By contrast, montelukast had no effect on sensitivity to mannitol and the PD₁₅ was 71 [36, 144] mg versus placebo (87 [51, 148] mg (p = 0.35). The total dose of mannitol delivered and the final percent reduction in FEV₁ with montelukast were 171 ± 142 mg and 21 ± 4% and for placebo were 182 ± 144 mg and 20 ± 5% (p = 0.35, p = 0.59, respectively). However, recovery of FEV₁ to baseline was faster with montelukast, with the area under the percent reduction FEV₁-versus-time curve reduced (220 ± 121% change·min) compared with placebo (513 ± 182% change·min) (p < 0.001). We conclude that whereas histamine is important for the initial airway response, leukotrienes are important in sustaining the airway response to inhaled mannitol.

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