Montelukast adult (10-mg film-coated tablet) and pediatric (5-mg chewable tablet) dose selections

Abstract

Montelukast is a selective leukotriene receptor antagonist that has been shown to be effective in the treatment of chronic asthma. It is approved in more than 70 countries for patients 6 years of age and older. For adults (> or = 15 years of age), a 10-mg film-coated tablet (FCT) is available, and for children (aged 6 to 14 years), a 5-mg chewable tablet (CT) is available. The adult montelukast dose (10-mg FCT) was selected on the basis of classic dose-ranging studies as the lowest dose that produces maximal improvement in both measures of airway function and patient-reported outcomes in chronic asthma and in the attenuation of exercise-induced bronchoconstriction. The strategy used for the pediatric dose selection for montelukast was based on the determination of a CT dose that would provide an overall systemic exposure to montelukast in children similar to that in adults who receive a 10-mg FCT dose. Because montelukast was to be given chronically for the treatment of asthma, the area under the plasma concentration-time curve was considered to be the pharmacokinetic measurement that best represented systemic exposure to the drug. A 5-mg CT yielded a comparable single-dose area under the plasma concentration-time curve profile to that of the adult 10-mg FCT dose and, therefore, was selected as the pediatric dose for children aged 6 to 14 years with asthma. Subsequently, 2 studies of efficacy and tolerability validated the choice of the 5-mg CT dose.