Applying Modeling and Simulations for Rational Dose Selection of Novel Toll‐Like Receptor 7/8 Inhibitor Enpatoran for Indications of High Medical Need

Autor: Lena, Klopp-Schulze, Jamie V, Shaw, Jennifer Q, Dong, Akash, Khandelwal, Cristina, Vazquez-Mateo, Kosalaram, Goteti
Rok vydání: 2022
Předmět:
Zdroj: Clinical Pharmacology & Therapeutics. 112:297-306
ISSN: 1532-6535
0009-9236
DOI: 10.1002/cpt.2606
Popis: Dual toll-like receptor (TLR) 7 and TLR8 inhibitor enpatoran is under investigation as a treatment for lupus and coronavirus disease 2019 (COVID-19) pneumonia. Population pharmacokinetic/pharmacodynamic (PopPK/PD) model-based simulations, using PK and PD (inhibition of ex vivo-stimulated interleukin-6 (IL-6) and interferon-α (IFN-α) secretion) data from a phase I study of enpatoran in healthy participants, were leveraged to inform dose selection for lupus and repurposed for accelerated development in COVID-19. A two-compartment PK model was linked to sigmoidal maximum effect (E
Databáze: OpenAIRE
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