Montelukast dose selection in 6- to 14-year-olds: comparison of single-dose pharmacokinetics in children and adults.
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.
Knorr
B
B
Merck Research Laboratories, Rahway, NJ 07065, USA.
Larson
P
P
Nguyen
H H
HH
Holland
S
S
Reiss
T F
TF
Chervinsky
P
P
Blake
K
K
van Nispen
C H
CH
Noonan
G
G
Freeman
A
A
Haesen
R
R
Michiels
N
N
Rogers
J D
JD
Amin
R D
RD
Zhao
J
J
Xu
X
X
Seidenberg
B C
BC
Gertz
B J
BJ
Spielberg
S
S
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
D000085:Acetates; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D013607:Tablets; D013608:Tablets, Enteric-Coated; C093875:montelukast