Comparison of the effects of intravenous and oral montelukast on airway function: a double blind, placebo controlled, three period, crossover study in asthmatic patients

Background-Montelukast, a leukotriene receptor antagonist, improves paramet ers of asthma control including forced expiratory volume in one second (FEV 1,) when given orally to patients aged six years or older. This study was u ndertaken to compare the effect on FEV1 of intravenous and oral montelukast and placebo during the 24 hour period following administration. Methods-Fifty one asthmatic patients (FEV1 40-80% predicted and greater tha n or equal to 15% improvement after inhaled beta agonist) were enrolled in a double blind, single dose, three period, crossover study to receive intra venous montelukast (7 mg), oral montelukast (10 mg), or placebo in a random ised fashion. The primary end point was area under the curve (AUG)(0-24 h) of the percentage change from baseline in FEV1. Additional end points were maximum percentage change in FEV1 and percentage change at different time p oints. Results-Compared with placebo, intravenous and oral montelukast significant ly increased the AUG(0-24 h) (means of 20.70%, 15.72%, and 7.75% for intrav enous, oral and placebo, respectively; no statistical difference between in travenous and oral). The difference in least square means from placebo for intravenous montelukast was 13.27% (95% CI 7.07 to 19.46), p<0.001 and for oral montelukast was 7.44% (95% CI 1.20 to 13.68), p = 0.020. The maximum p ercentage change in FEV1 was nor significantly different for intravenous an d oral montelukast (difference in least square means 6.78% (95% CI-0.59 to 14.15), p 0.071). The mean percentage change in FEV1 for intravenous montel ukast was greater than for oral montelukast within the first hour (15.02% v s 4.67% at 15 min, p less than or equal to 0.001; 18.43% vs 12.90% at one h our, p<0.001 for intravenous and oral montelukast, respectively (placebo 3. 05% at 15 minutes, 7.33% at one hour). Intravenous and oral montelukast wer e similar to placebo in the frequency of adverse events, Conclusions-The onset of action for intravenous montelukast was faster than for oral montelukast and the improvement in airway function lasted over th e 24 hour observation period for both treatments. Although not well underst ood, there was a trend toward a greater improvement: in FEV1 with intraveno us than with oral montelukast. These findings suggest. that leukotriene rec eptor antagonists should be investigated as a treatment for acute severe as thma.