Physiologically Based Pharmacokinetic Modeling of Clobazam and Stiripentol Co-Therapy in Dravet Syndrome.

ABSTRACT: Background: Dravet syndrome, a severe early-onset epileptic encephalopathy, is treated with multiple antiepileptic drugs such as clobazam (CLB) and stiripentol (STP), increasing the risk of drug-drug interactions (DDIs). Given the limited pediatric pharmacokinetic data, this study developed physiologically based pharmacokinetic (PBPK) models for CLB and STP to optimize dosing and assess DDI risk across pediatric age groups. Methods: We developed PBPK models for CLB, its active metabolite, N-desmethylclobazam (N-CLB), and STP in healthy adults and pediatric patients with Dravet syndrome aged two years and older. We evaluated the inhibitory effect of STP on CLB and N-CLB metabolism, accounting for CYP2C19 phenotypes. The model was extrapolated to predict drug exposure in

SUBMITTER: Eltanameli B 

PROVIDER: S-EPMC12653854 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature