Leukotriene receptor antagonists

Placebo-controlled studies

The efficacy and tolerability of montelukast, in combination with a selective histamine H ₁ receptor antagonist (loratadine), has been investigated in a randomized, double-blind, crossover study for 2 weeks in 125 asthmatic subjects (mean FEV ₁ 67% predicted), who took montelukast 10 mg plus loratadine 20 mg or placebo od for 2 weeks [ ]. The subjects were symptomatic, in that their mean baseline daily use of beta ₂ -adrenoceptor agonists was 5.1 inhaled metered doses. During the study, the percentage increase in FEV ₁ from baseline was significantly greater with montelukast plus loratadine than with montelukast alone (14% versus 9.7%). The most common adverse events during the trial were headache and upper respiratory tract infection (each in about 10% of subjects). There were no significant differences in the frequencies of adverse experiences between montelukast plus loratadine and montelukast alone. Ten patients withdrew because of an adverse event; six had exacerbation of asthma requiring steroid administration (three in each of the two arms of the study). One patient taking montelukast plus loratadine and four taking montelukast alone had transient self-limiting laboratory abnormalities.

The acute effects of intravenous and oral montelukast on airway function have been compared in a randomized, double-blind, crossover study in 51 asthmatic patients (mean FEV ₁ 63.8% predicted) [ ]. The intravenous dose (7 mg) was known to produce a comparable AUC to that obtained with an oral dose of 10 mg. FEV ₁ was measured at 0.25,0.5,1, and 2 hours and then at regular intervals up to 24 hours after dosing. After intravenous and oral montelukast, the FEV ₁ AUC _{0 ⟶ 24} was significantly greater than after placebo (mean increases 21%, 16%, and 7.8% for intravenous, oral, and placebo respectively). The mean percentage change in FEV ₁ for intravenous montelukast was greater than for oral montelukast in the first hour (18% versus 13%). The most frequently reported adverse events included headaches, which occurred in three patients taking placebo, four taking oral montelukast, and one taking intravenous montelukast. Influenza was reported in two patients taking placebo. It was noteworthy that there were no local adverse events at the intravenous site of the montelukast administration. This study has raised the possibility that a bolus dose of intravenous montelukast may have a role in the management of acute exacerbations of asthma.