Model-Informed Drug Development for Everolimus Dosing Selection in Pediatric Infant Patients.

ABSTRACT: Everolimus is currently approved in Europe as an adjunctive therapy for patients aged ≥ 2 years with tuberous sclerosis complex (TSC)-associated treatment-refractory partial-onset seizures, based on the EXIST-3 study (NCT01713946) results. As TSC-associated seizures can also affect children aged between 6 months and 2 years, a modeling and simulation (M&S) approach was undertaken to extrapolate exposure (trough plasma concentration (C_min )) after a dose of 6 mg/m² and reduction in seizure frequency (RSF). A physiologically based pharmacokinetic model using Simcyp was developed to predict C_min in adult and pediatric patients, which was then used by a population pharmacodynamic model and a linear mixed effect model to predict short-term and long-term efficacy

SUBMITTER: Combes FP 

PROVIDER: S-EPMC7180003 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature