Population pharmacokinetics, enzyme occupancy, and 24S‐hydroxycholesterol modeling of soticlestat, a novel cholesterol 24‐hydroxylase inhibitor, in healthy adults

• Published in: Clinical and translational science Vol. 16; no. 7; pp. 1149 - 1162
• Main Authors: Yin, Wei, Facius, Axel, Wagner, Thomas, Tsai, Max, Asgharnejad, Mahnaz, Lahu, Gëzim, Vakilynejad, Majid
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.07.2023; John Wiley and Sons Inc; Wiley
• Subjects: Administration, Oral; Adult; Bioavailability; Child; Cholesterol; Cholesterol 24-Hydroxylase; Clinical trials; Design optimization; Dosage; Drug dosages; Enzymes; Epilepsy; Humans; Metabolism; Metabolites; Models, Biological; Oral administration; Pediatrics; Pharmacodynamics; Pharmacokinetics; Plasma; Simulation

Soticlestat is a first‐in‐class, selective inhibitor of cholesterol 24‐hydroxylase (CH24H), which catabolizes cholesterol to 24S‐hydroxycholesterol (24HC) in the brain, in phase III development for Dravet syndrome and Lennox–Gastaut syndrome treatment. This study aimed to develop a model of soticles...