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

This study aimed to build a physiologically based pharmacokinetic (PBPK) model coupled with age-appropriatein 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-appropriatein 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 descrip tion ofin vivo drug performance in adults and children. For case study 2, a good description ofin vivo drug performance in infants after medicine co-administration with vehicles was achieved by incorporatingin vitro drug dissolution (under simulated fasted gastric to fed intestinal conditions) into a fed state PBPK model with consideration of thein vivo dosing conditions (mixing of formulation with applesauce or formula). The case studies presented demonstrate how a ...
Source: The AAPS Journal - Category: Drugs & Pharmacology Source Type: research