Physiologically Based Pharmacokinetic Modeling to Predict Drug-Drug Interactions of Soticlestat as a Victim of CYP Induction and Inhibition, and as a Perpetrator of CYP and P-Glycoprotein Inhibition.

ABSTRACT: Soticlestat (TAK-935) is a cholesterol 24-hydroxylase inhibitor. A physiologically-based pharmacokinetic model has been developed to predict potential soticlestat drug-drug interactions (DDIs) using the Simcyp v20 Population-based Simulator and verified with data from single-/multiple-rising-dose and clinical DDI studies. Simulated area under the plasma concentration-time curve from 0 to infinity (AUC_0-inf) and maximal drug concentration (C_max) based on the model were generally within 2-fold of observed values for all soticlestat doses. Model-simulated versus observed AUC_0-inf and C_max geometric mean ratios (GMRs) for soticlestat with/without itraconazole (potent cytochrome P450 [CYP] 3A inhibitor), and mefenamic acid (potent UDP glucuronosyltran

SUBMITTER: Jia H 

PROVIDER: S-EPMC12044326 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature