RESUMEN
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.
Asunto(s)
Acetatos/administración & dosificación , Acetatos/farmacocinética , Antiasmáticos/administración & dosificación , Asma/tratamiento farmacológico , Quinolinas/administración & dosificación , Quinolinas/farmacocinética , Acetatos/efectos adversos , Acetatos/uso terapéutico , Adulto , Antiasmáticos/efectos adversos , Antiasmáticos/farmacocinética , Antiasmáticos/uso terapéutico , Área Bajo la Curva , Niño , Preescolar , Ciclopropanos , Formas de Dosificación , Femenino , Humanos , Antagonistas de Leucotrieno/administración & dosificación , Antagonistas de Leucotrieno/efectos adversos , Antagonistas de Leucotrieno/farmacocinética , Antagonistas de Leucotrieno/uso terapéutico , Masculino , Quinolinas/efectos adversos , Quinolinas/uso terapéutico , SulfurosRESUMEN
BACKGROUND: Montelukast, a leukotriene receptor antagonist, and salmeterol, a long-acting beta(2)-receptor agonist, each have demonstrated benefits in the treatment of exercise-induced bronchoconstriction (EIB) in short-term studies. Direct comparisons between these agents in long-term studies are limited. OBJECTIVE: We sought to compare montelukast and salmeterol in the long-term treatment of EIB. METHODS: One hundred ninety-seven patients with mild asthma and a postexercise fall in FEV(1) of at least 18% were randomized (double-blind) to receive montelukast 10 mg once daily or salmeterol 50 microg twice daily for 8 weeks. Exercise challenge was repeated at day 3, week 4, and week 8 after randomization near the end of the dosing interval for both drugs. The primary efficacy endpoint was the maximal percent fall in postexercise FEV(1) at week 8. RESULTS: Montelukast was effective in treating EIB without inducing tolerance and provided superior (P =.001) protection than salmeterol at weeks 4 and 8, with comparable protection at day 3. The frequency of respiratory clinical adverse events (P =.046) and discontinuations because of clinical adverse events (P =.052) were less with montelukast. CONCLUSION: The effect of montelukast was greater than that of salmeterol in the chronic treatment of EIB over a period of 8 weeks in patients with mild asthma as demonstrated by effect size, maintenance of effect, and fewer respiratory clinical adverse events during the study period. Montelukast may be a better alternative to salmeterol as a controller agent for the chronic treatment of EIB.
Asunto(s)
Acetatos/uso terapéutico , Albuterol/análogos & derivados , Asma Inducida por Ejercicio/tratamiento farmacológico , Broncodilatadores/uso terapéutico , Quinolinas/uso terapéutico , Adolescente , Adulto , Albuterol/uso terapéutico , Enfermedades Bronquiales/tratamiento farmacológico , Constricción Patológica , Ciclopropanos , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Xinafoato de Salmeterol , Método Simple Ciego , SulfurosRESUMEN
BACKGROUND: Oral leukotriene receptor antagonists have been shown to have efficacy in chronic asthma. OBJECTIVE: To compare the clinical benefit of montelukast, a once-daily oral leukotriene receptor antagonist; placebo; and inhaled beclomethasone. DESIGN: Randomized, double-blind, double-dummy, placebo-controlled, parallel-group, 12-week study. SETTING: 36 sites worldwide. PATIENTS: 895 patients 15 to 85 years of age with chronic asthma and an FEV1 50% to 85% of predicted. INTERVENTIONS: Montelukast, 10 mg once daily at bedtime; inhaled beclomethasone, 200 microg twice daily, administered with a spacer device; or placebo. MEASUREMENTS: Primary end points were daytime asthma symptom score and FEV1. Secondary end points were peak expiratory flow rates in the morning and evening, as-needed beta-agonist use, nocturnal awakenings, asthma-specific quality of life, and worsening asthma episodes. RESULTS: Over the 12-week treatment period, the average percentage change from baseline in FEV1 was 13.1% with beclomethasone, 7.4% with montelukast, and 0.7% with placebo (P < 0.001 for each active treatment compared with placebo; P < 0.01 for beclomethasone compared with montelukast). The average change from baseline in daytime symptom score was -0.62 for beclomethasone, -0.41 for montelukast, and -0.17 for placebo (P < 0.001 for each active treatment compared with placebo; P < 0.01 for beclomethasone compared with montelukast). Each agent improved peak expiratory flow rates and quality of life, reduced nocturnal awakenings and asthma attacks, increased the number of asthma-control days, and decreased the number of days with asthma exacerbations (P < 0.001 for each active treatment compared with placebo for each end point; P < 0.01 for beclomethasone compared with montelukast for each end point). Although beclomethasone had a greater mean clinical benefit than montelukast, montelukast had a faster onset of action and a greater initial effect. The two agents caused similar decreases in peripheral blood eosinophil counts (P < 0.05 for each agent compared with placebo). Both agents had tolerability profiles similar to that of placebo over the 12-week study. CONCLUSIONS: Although beclomethasone had a larger mean effect than montelukast, both drugs provided clinical benefit to patients with chronic asthma. This finding is consistent with the use of these agents as controller medications for chronic asthma.