[Clinical effects of montelukast sodium in treatment of allergic rhinetis in children]

[Article in Chinese]

Wang WQ.

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A population pharmacokinetic model for montelukast disposition in adults and children.

Knorr B.

Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania, USA. rohini_ramakrishnan merck.com

PURPOSE: The purpose was to develop a population pharmacokinetic model for montelukast after intravenous administration. Clinical trial simulations were conducted using the model developed to identify the lowest intravenous dose in 6- to 14-year-old children that would give montelukast systemic exposures that were comparable to those found to be associated with efficacy in adults. METHODS: Two clinical studies were conducted where montelukast was administered intravenously as a 7-mg dose to adults and as a 3.5-mg dose to children aged 6 to 14 years. Model development included defining the base pharmacostatistical model and investigating the effects of demographic variables [age and total body weight (TBW)] on the structural parameters, using a nonlinear mixed effect modeling approach. RESULTS: A linear three-compartment pharmacokinetic model was found to best describe the disposition of montelukast. Inclusion of TBW as a covariate caused a 35% and 63% decrease in the interindividual variabilities on clearance and central volume of distribution, respectively. Trial simulations suggested that a 5.25-mg intravenous dose of montelukast should be chosen in children aged 6 to 14 years. CONCLUSIONS: The model developed can adequately describe the intravenous pharmacokinetics of montelukast and can be used as a useful tool for dose selection in pediatric subpopulations.

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[The effect of montelukast, a leukotriene antagonist, on improvement of exercise-induced bronchoconstriction.]

[Article in Chinese]

Ming SH.

Department of Respiratory Medicine, Beijing Hospital, Beijing 100730, China.

OBJECTIVE: To study the efficacy of montelukast, a cysteinyl leukotriene receptor antagonist, in the treatment and prevention of exercise-induced bronchoconstriction (EIB) in mild asthmatic patients and patients with exercise-induced asthma (EIA). METHODS: Thirty mild asthmatic patients with positive standardized exercise challenge test were enrolled. The subjects received montelukast 10 mg once daily in the evening. Standard exercise challenge was performed before, three days and twenty-eight days after the administration of the drug. The end points included: (1) Area under the percent fall in forced expiratory volume in one second (FEV1) versus time curve (AUC0 to approximately 60 min); (2) Time of recovery to within 5% of the pre-exercise baseline FEV1 value; and (3) Maximal percent fall in FEV1 from pre-exercise baseline. RESULTS: Montelukast caused significant reduction in AUC0 to approximately 60 min, which was (39 +/- 21)%.min before treatment as compared to (13 +/- 14)%.min and (12 +/- 14)%.min three days and twenty-eight days respectively after the treatment with montelukast. Time of recovery to within 5% of the pre-exercise baseline FEV1 value were (51 +/- 36) min, (26 +/- 28) min and (25 +/- 33) min respectively. The mean maximal percentage decrease in FEV1 after exercise was 44.4% before treatment, 26.8% and 18.2% following montelukast. FEV1 and peak expiratory flow rate (PEFR) were maintained to nearly normal during all the study. Inhale corticosteroid did not prevent EIB/EIA. CONCLUSION: Montelukast attenuates and protects against EIB/EIA.

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[Single dose of montelukast as an effective prevention of post exercise bronchospasm in children with bronchical asthma.]

[Article in Polish]

Janiak B.

Centrum Pulmonologii i Alergologii, Mysliwska 13, 58-540 Karpacz, Poland. gaszczyk poczta.onet.pl.

Post exercise bronchospasm is a well-known phenomenon, particularly affecting children with asthma. In our own study post exercise bronchospasm occurred in 25-66% of children with asthma. The aim of the study was to evaluate the usefulness of cysteinyl leukotriene receptor antagonist - montelukast (Mnt) in the prevention of post exercise bronchospasm. Material and methods: we studied 72 children 7-14 years old (22 girls. 50 boys) mean age - 10.8+/- 2.4 (SD), who were suffering from asthma. All children with forced expiratory volume in one second (FEV1) >70% of the predicted value and a reproducible fall in FEV1 after exercise of at least 15% were enrolled. After a screening test was performed the children were divided in 2 subgroups: 40 children for active treatment - monte1ukast, 32 for placebo group. Placebo or monetlukast (5 mg) was given once in the evening, randomised, double blind. Next day 3 bronchial provocation tests at 8 a.m., 12 a.m. and 3 p.m. were performed. Data from 72 patients were available for complete analysis of the following parameters: forced expiratory volume in one second (FEV1), peak expiratory flow (PEF) forced expiratory flow at 25 and 75 of forced vital capacity (FEF 25-75%). Results: Analysis showed a significant total protective effect 12 h after giving montelukast in 25/40 (62.5%) children, but only in 4/32 (12.5%) in the placebo group, (OR=1.87). Partial protection was detected in 3/40 (7.5%) children in montelukast group and in 1/32 (3.3%) child in placebo group. Lack of protection was observed in 12/40 (30%) in montelukast group and in 27/42 (84.4%) in the placebo group. Conclusions: l. The clinically recommended dose of montelukast protects against post exercise induced bronchospasm. 2. The time of duration of montelukast as protective treatment of post exercise bronchospam was at least 21 hours. 3. Our study may suggest the participation of leukotrienes in the pathogenesis of exercise-induced bronchocontriction.

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Validation of a pediatric caregiver diary to measure symptoms of postacute respiratory syncytial virus bronchiolitis.

Bisgaard H.

Merck Research Laboratories, West Point, Pennsylvania.

Acute respiratory syncytial virus (RSV)-induced bronchiolitis is often associated with continuing respiratory symptoms following hospitalization. To date, there is no validated objective measure to evaluate symptoms of RSV-induced bronchiolitis. We report on the reliability, validity, and responsiveness of the bronchiolitis caregiver diary (BCD) of symptoms and healthcare utilization associated with postacute RSV. The BCD measures four symptoms (daytime cough, wheeze, trouble breathing, and nighttime cough), healthcare utilization, and rescue medication for worsening of lung symptoms. Data from the 4-week treatment period of the reported prospective, placebo-controlled trial of montelukast for treatment of postacute RSV were used to assess reliability (internal consistency and test-retest), construct validity (cross-sectional and longitudinal correlations), discriminant validity (known-groups analyses), and responsiveness. The primary outcome of this study was the percentage of symptom-free days (SFD). The secondary outcome was a composite symptom score (CSS; average of daytime cough, wheezing, and trouble breathing). Cronbach's alpha of 0.85 indicated that the four symptoms were internally consistent, supporting a unidimensional scale structure. Test-retest reliabilities for the percentage of SFD and CSS were above the recommended cut point of 0.70. Cross-sectional and longitudinal correlations were sizeable and statistically significant, demonstrating construct validity. Hypothesized known-group differences were statistically significant in the appropriate direction. Responsiveness analyses indicated moderate effect sizes for percentage of SFD. In conclusion, the BCD provides a valid, reliable, and responsive tool for the assessment of symptoms of postacute RSV-induced bronchiolitis, capable of measuring moderate effect sizes, and demonstrating responsiveness to therapy. (c) 2005 Wiley-Liss, Inc.

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