Pharmacokinetics and Safety of Montelukast Oral Granules in Children 1 to 3 Months of Age With Bronchiolitis

Kearns, Gregory L.; Lu, Susan; Maganti, Lata; Li, Xiujiang Susie; Migoya, Elizabeth; Ahmed, Tuli; Knorr, Barbara; Reiss, Theodore F.

doi:10.1177/0091270008314251

Cited by 27 publications

(34 citation statements)

References 32 publications

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“…Off-label use is common in children older than 1 month suffering from recurrent wheezing. In a clinical trial, a dose of 1-2 mg/kg of body weight was given to full-term born infants at 1 month of age with no side effects [19]. …”

Section: Introductionmentioning

confidence: 99%

Leukotriene Receptor Blockade as a Life-Saving Treatment in Severe Bronchopulmonary Dysplasia

Rupprecht¹,

Rupprecht

Harms³

et al. 2014

Respiration

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Background: Bronchopulmonary dysplasia (BPD) is a major cause of mortality and morbidity in infants with an extremely low birth weight. Because there is no effective therapy, the mortality of this condition in severely affected patients is high. Therapeutic blocking of the leukotriene system seems to be a logical approach due to the known pathophysiology of BPD. Objectives: The aim of this study was to examine the therapeutic effect of montelukast in preterm children suffering from severe BPD. Methods: We performed an unblinded, prospective trial including infants born between 23 and 27 weeks of gestation suffering from severe BPD. The study drug was montelukast (1 mg/kg of body weight as a single dose daily in the 1st week of therapy, increasing to 1.5 mg/kg of body weight in the 2nd week and finally to 2 mg/kg of body weight in the 3rd week). Treatment was continued until the radiological signs and the clinical symptoms of BPD disappeared or the patient was discharged from the hospital. Each patient included in this study was matched for gestational age, birth weight, and pulmonary severity score to a control. Results: Until March 2014, a total of 22 infants were enrolled into the study. The rates of the primary outcome differed significantly between the montelukast-treated group and the control group. All but 1 of the children in the treatment group survived (91%), whereas 7 of the 11 children in the control group died (survival rate 36%; p = 0.002 using Fisher's exact test). The mean mechanical ventilation time (41.2 ± 25.3 vs. 103.7 ± 90.6 days) was significantly shorter and the mean preterm complication score (3.0 ± 1.7 vs. 5.6 ± 1.4) was significantly lower in treated patients compared to the control group. (p = 0.05 for both items; Wilcoxon's matched-pairs test). Conclusion: Based on the clinical observations, the statistical results, and the relatively low risk of the study drug montelukast, we recommend using this treatment in severe cases of BPD for infants facing a high risk of death.

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Section: Introductionmentioning

confidence: 99%

Leukotriene Receptor Blockade as a Life-Saving Treatment in Severe Bronchopulmonary Dysplasia

Rupprecht¹,

Rupprecht

Harms³

et al. 2014

Respiration

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“…Several population pharmacokinetic blood sampling designs could have been used, but we chose to use a sparse sampling technique with mixed-effect modelling in order to minimise the number of blood samples required from each participant. This methodology is particularly attractive for paediatric pharmacokinetic studies [24, 25, 37, 38]. With this design, children are allocated to one of several blood sampling schemes, such that the entire dosing interval is sampled but no one child is subjected to blood sampling at each time-point.…”

Section: Discussionmentioning

confidence: 99%

Bioavailability of inhaled fluticasone propionate via chambers/masks in young children

Blake

Mehta

Spencer³

et al. 2011

European Respiratory Journal

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We determined lung bioavailability of a fluticasone propionate (FP) pressurised metred-dose inhaler (Flovent® HFA; GlaxoSmithKline, Research Triangle Park, NC, USA) administered via AeroChamber Plus® (Monaghan Medical, Plattsburgh, NY, USA) with Facemask and Babyhaler® (GlaxoSmithKline) valved holding chambers (VHCs) using a population pharmacokinetic approach. Children from 1 to <4 yrs of age with stable asthma but a clinical need for inhaled corticosteroid therapy were administered 88 µg FP hydrofluoroalkane (2 × 44 µg) twice daily delivered through the two devices in an open-label, randomised crossover manner for 8 days each. Patients were randomised to one of three sparse sampling schedules for blood collection throughout the 12-h dosing interval on the 8th day of each treatment for pharmacokinetic analysis. The area under the FP plasma concentration–time curve (AUC) was determined for each regimen. 17 children completed the study. The population mean AUC following FP with AeroChamber Plus® with Facemask was 97.45 pg·h·mL−1 (95% CI 85.49–113.32 pg·h·mL−1) and with Babyhaler® was 51.55 pg·h·mL−1 (95% CI 34.45–64.46 pg·h·mL−1). The relative bioavailability (Babyhaler®/AeroChamber Plus®) was 0.53 (95% CI 0.30–0.75). Clinically significant differences in lung bioavailability were observed between the devices. VHCs are not interchangeable, as differences in drug delivery to the lung may occur. A population pharmacokinetic approach can be used to determine lung bioavailability of FP.

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“…33,[36][37][38][39][40][41][42][43][44][45] Serious adverse events, such as worsening asthma, appear to be rare 46 and all reported patients with drug overdoses recovered without sequelae. 46 Less serious side effects of montelukast occur uncommonly, but may include pharyngitis, dizziness, nausea, headache, diarrhea, fever, abdominal pain and rash.…”

Section: Safetymentioning

confidence: 99%

Montelukast Sodium: Administration to Children to Control Intermittent Asthma

2010

Clinical Medicine Reviews in Therapeutics

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The prototype cysteinyl leukotriene receptor antagonist, montelukast, is generally considered to have a niche application in the chemotherapy of exercise-induced asthma. It has also been used as add-on therapy in patients whose asthma is poorly controlled with inhaled corticosteroid monotherapy, or with the combination of a long-acting β(2)-agonist and an inhaled corticosteroid. Recently, however, montelukast has been reported to possess secondary anti-inflammatory properties, apparently unrelated to conventional antagonism of cysteinyl leukotriene receptors. These novel activities enable montelukast to target eosinophils, monocytes, and, in particular, the corticosteroid-insensitive neutrophil, suggesting that this agent may have a broader spectrum of anti-inflammatory activities than originally thought. If so, montelukast is potentially useful in the chemotherapy of intermittent asthma because most exacerbations of this condition involve respiratory virus infection-triggered inflammatory mechanisms which, to a large extent, involve airway epithelial cell/neutrophil interactions. The primary objective of this review is to evaluate the role of montelukast in the treatment of intermittent asthma in children.

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Pharmacokinetics and Safety of Montelukast Oral Granules in Children 1 to 3 Months of Age With Bronchiolitis

Cited by 27 publications

References 32 publications

Leukotriene Receptor Blockade as a Life-Saving Treatment in Severe Bronchopulmonary Dysplasia

Leukotriene Receptor Blockade as a Life-Saving Treatment in Severe Bronchopulmonary Dysplasia

Bioavailability of inhaled fluticasone propionate via chambers/masks in young children

Montelukast Sodium: Administration to Children to Control Intermittent Asthma

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