Fexofenadine decreases sensitivity to and montelukast improves recovery from inhaled mannitol.
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 PD(15) was (mean [95% confidence interval] 138 [95, 201]) mg versus placebo (51 [25, 106] mg) (p < 0.001). The final percent reduction in FEV(1) 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 PD(15) 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 FEV(1) 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 FEV(1) to baseline was faster with montelukast, with the area under the percent reduction FEV(1)-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.
Brannan
J D
JD
Department of Respiratory Medicine, PCP9, Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW 2006, Australia.
Anderson
S D
SD
Gomes
K
K
King
G G
GG
Chan
H K
HK
Seale
J P
JP
D000085:Acetates / Q000276:immunology / Q000627:therapeutic use*; D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000276:immunology / Q000627:therapeutic use*; D001249:Asthma / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D001985:Bronchial Provocation Tests / Q000379:methods*; D003521:Cyclopropanes; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006634:Histamine H1 Antagonists / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D020024:Leukotriene Antagonists / Q000276:immunology / Q000627:therapeutic use*; D008297:Male; D008353:Mannitol; D008875:Middle Aged; D011804:Quinolines / Q000276:immunology / Q000627:therapeutic use*; D020127:Recovery of Function / Q000187:drug effects; D013440:Sulfides; D016593:Terfenadine / Q000031:analogs & derivatives* / Q000276:immunology / Q000627:therapeutic use*; D013997:Time Factors
D000085:Acetates; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D006634:Histamine H1 Antagonists; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D008353:Mannitol; D016593:Terfenadine; C093230:fexofenadine; C093875:montelukast