Performance Evaluation of Montelukast Pediatric Formulations: Part II — a PBPK Modelling Approach

Mariana Guimarães, Maria Vertzoni, Nikoletta Fotaki

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2 Citations (SciVal)


This study aimed to build a physiologically based pharmacokinetic (PBPK) model coupled with age-appropriate in vitro dissolution data to describe drug performance in adults and pediatric patients. Montelukast sodium was chosen as a model drug. Two case studies were investigated: case study 1 focused on the description of formulation performance from adults to children; case study 2 focused on the description of the impact of medicine co-administration with vehicles on drug exposure in infants. The PBPK model for adults and pediatric patients was developed in Simcyp® v18.2 informed by age-appropriate in vitro dissolution results obtained in a previous study. Oral administration of montelukast was simulated with the ADAM™ model. For case study 1, the developed PBPK model accurately described montelukast exposure in adults and children populations after the administration of montelukast chewable tablets. Two-stage dissolution testing in simulated fasted gastric to intestinal conditions resulted in the best description of in vivo drug performance in adults and children. For case study 2, a good description of in vivo drug performance in infants after medicine co-administration with vehicles was achieved by incorporating in vitro drug dissolution (under simulated fasted gastric to fed intestinal conditions) into a fed state PBPK model with consideration of the in vivo dosing conditions (mixing of formulation with applesauce or formula). The case studies presented demonstrate how a PBPK absorption modelling strategy can facilitate the description of drug performance in the pediatric population to support decision-making and biopharmaceutics understanding during pediatric drug development. Graphical abstract: [Figure not available: see fulltext.].

Original languageEnglish
Article number27
JournalAAPS Journal
Issue number1
Publication statusPublished - 10 Jan 2022

Bibliographical note

Funding Information:
This work was supported by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No 674909 (PEARRL), .


  • age-related dissolution
  • biopharmaceutics
  • montelukast
  • oral absorption
  • pediatrics
  • physiologically based pharmacokinetic (PBPK) modelling

ASJC Scopus subject areas

  • Pharmaceutical Science


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