title: Montelukast dose selection in 6- to 14-year-olds: comparison of single-dose pharmacokinetics in children and adults.
abstract: Montelukast, an oral leukotriene-receptor antagonist, has demonstrated efficacy and tolerability for the treatment of chronic asthma in adults. A once-daily 10 mg dose (film-coated tablet) was selected as the optimal adult dose based on dose-ranging studies. Asthma is a similar disease and is treated with the same medications in children and adults. These observations suggested that a dose of montelukast in children providing overall drug exposure (i.e., montelukast plasma concentrations) similar to that of the 10 mg film-coated tablet dose in adults would be efficacious, well tolerated, and obviate the need for separate dose-ranging studies in children. Therefore, the dose of montelukast for 6- to 14-year-old children was selected by identifying the chewable tablet dose of montelukast yielding a single-dose area under the plasma concentration-time curve (AUC) comparable to that achieved with the adult 10 mg film-coated tablet dose. Based on this approach, which included dose normalization of data from several pediatric pharmacokinetic studies, a 5 mg chewable tablet dose of montelukast was selected for use in clinical efficacy studies in 6- to 14-year-old children with asthma.
authors.affiliation: Merck Research Laboratories, Rahway, NJ 07065, USA.
authors.forename: B
authors.initials: B
authors.lastname: Knorr
authors.forename: P
authors.initials: P
authors.lastname: Larson
authors.forename: H H
authors.initials: HH
authors.lastname: Nguyen
authors.forename: S
authors.initials: S
authors.lastname: Holland
authors.forename: T F
authors.initials: TF
authors.lastname: Reiss
authors.forename: P
authors.initials: P
authors.lastname: Chervinsky
authors.forename: K
authors.initials: K
authors.lastname: Blake
authors.forename: C H
authors.initials: CH
authors.lastname: van Nispen
authors.forename: G
authors.initials: G
authors.lastname: Noonan
authors.forename: A
authors.initials: A
authors.lastname: Freeman
authors.forename: R
authors.initials: R
authors.lastname: Haesen
authors.forename: N
authors.initials: N
authors.lastname: Michiels
authors.forename: J D
authors.initials: JD
authors.lastname: Rogers
authors.forename: R D
authors.initials: RD
authors.lastname: Amin
authors.forename: J
authors.initials: J
authors.lastname: Zhao
authors.forename: X
authors.initials: X
authors.lastname: Xu
authors.forename: B C
authors.initials: BC
authors.lastname: Seidenberg
authors.forename: B J
authors.initials: BJ
authors.lastname: Gertz
authors.forename: S
authors.initials: S
authors.lastname: Spielberg
mesh_terms: D000085:Acetates / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism; D002648:Child; D003521:Cyclopropanes; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006207:Half-Life; D006801:Humans; D020024:Leukotriene Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D011804:Quinolines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013440:Sulfides; D013607:Tablets; D013608:Tablets, Enteric-Coated; D016896:Treatment Outcome
chemical_list: D000085:Acetates; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D013607:Tablets; D013608:Tablets, Enteric-Coated; C093875:montelukast