A population pharmacokinetic model for montelukast disposition in adults and children

The purpose was to develop a population pharmacokinetic model for montelukast after intravenous administration. Clinical trial simulations were conducted using the model developed to identify the lowest intravenous dose in 6- to 14-year-old children that would give montelukast systemic exposures that were comparable to those found to be associated with efficacy in adults.

Two clinical studies were conducted where montelukast was administered intravenously as a 7-mg dose to adults and as a 3.5-mg dose to children aged 6 to 14 years. Model development included defining the base pharmacostatistical model and investigating the effects of demographic variables [age and total body weight (TBW)] on the structural parameters, using a nonlinear mixed effect modeling approach.

A linear three-compartment pharmacokinetic model was found to best describe the disposition of montelukast. Inclusion of TBW as a covariate caused a 35% and 63% decrease in the interindividual variabilities on clearance and central volume of distribution, respectively. Trial simulations suggested that a 5.25-mg intravenous dose of montelukast should be chosen in children aged 6 to 14 years.

The model developed can adequately describe the intravenous pharmacokinetics of montelukast and can be used as a useful tool for dose selection in pediatric subpopulations.