No abstract

Montelukast, a leukotriene receptor antagonist, has demonstrated efficacy and tolerability in the treatment of asthma in patients age 6 years and older. The purpose of this open, one-period, multicenter population pharmacokinetic study was to identify a chewable tablet (CT) dose of montelukast for administration to children ages 2 to 5 years with asthma, yielding a single-dose pharmacokinetic profile (area under the plasma concentration-time curve [AUC]) comparable to that of the 10 mg film-coated tablet (FCT) dose in adults. Because patient numbers were small and the volume of blood that could be collected from individual 2- to 5-year-old patients was limited, a population pharmacokinetic approach was used to estimate population AUC (AUCpop). The 4 mg CT dose of montelukast was well tolerated and yielded an AUCpop (2721 ng.h/mL) similar to that of the adult AUCpop (2595 ng.h/mL) observed after a 10 mg FCT dose. These results support the selection of a 4 mg once-daily CT dose of montelukast for future efficacy and safety studies in children ages 2 to 5 years with asthma.

No abstract

The objective of this double-blind cross-over study was to evaluate montelukast for the prevention of exercise-induced bronchoconstriction (EIB). Sixty-two patients with EIB (post-exercise decrease in forced expiratory volume in 1 second (FEV(1)) > or = 20% at pre-randomization) were randomized to montelukast 10 mg or placebo, followed by exercise-challenge 2, 12, and 24 hours postdose. The primary endpoint was the maximum percent-fall in FEV(1) (from pre-exercise FEV(1)) during 60 minutes after exercise-challenge at 2 hours postdose. This endpoint was improved after montelukast (mean +/- SD = 11.7% +/- 10.8) versus placebo (17.5% +/- 13.8) (p < or = 0.001); numerically greater improvements were seen at 12 hours and 24 hours. A quicker time to recovery after challenge (p < or = 0.001) and a smaller area under the curve for percent-fall in FEV(1) during 60 minutes after challenge (p < or = 0.01) were seen with montelukast at 2 hours. At this timepoint, more patients taking montelukast (45/54) than taking placebo (37/54) were protected against EIB (p = 0.039). We concluded that montelukast provided significant protection against EIB at 2 hours after a single dose.

Single-dose montelukast attenuates exercise-induced bronchoconstriction (EIB) in adults within 2 hours postdose and lasting through 24 hours. This study evaluated the onset and duration of EIB attenuation in children after a single dose of montelukast. A randomized, double-blind, placebo-controlled, two-period crossover study was performed. Patients (n = 66) aged 4-14 years, with preexercise forced expiratory volume in 1 second of (FEV(1)) ≥70% predicted and maximum percentage fall in FEV(1) of ≥20% at two screening exercise challenges were eligible. Patients were to receive single-dose montelukast (4 or 5 mg) or placebo before performing standardized exercise challenges at 2 and 24 hours postdose. A 3- to-7-day washout separated the two crossover periods. The primary end point was maximum percentage fall in FEV(1) after exercise challenge 2 hours postdose. Secondary end points included maximum percentage fall in FEV(1) after the 24-hour postdose challenge; each of the following at 2 and 24 hours postdose-maximum percentage fall in FEV(1) categorized as <10%, 10-20%, or >20%; area under the curve (AUC) during 60 minutes postchallenge; time to recovery of FEV(1) to within 5% of preexercise baseline; and need for rescue medication. The mean maximum percentage fall in FEV(1) after the 2-hour postdose exercise challenge was significantly attenuated after single-dose montelukast compared with placebo (15.35% versus 20.00%; p = 0.020). Montelukast was also significantly more effective than placebo for maximum percentage fall after the 24-hour challenge (12.92% versus 17.25%; p = 0.005), the categorized maximum percent fall in FEV(1) at 2 hours (p = 0.034), and AUC at 2 hours (p = 0.022) and 24 hours (p = 0.013). Single-dose montelukast provided rapid and sustained EIB attenuation in children. Clinicaltrials.gov identifier: NCT00534976.