by Eriksson J, Sjögren E, Gillon JY, Caplain H, Goyal V, Satam V, Robinson S, Ribeiro I, Chenel M. CPT Pharmacometrics & Systems Pharmacology 2025, 14(4):651-657. doi: 10.1002/psp4.13309
Summary: This case study explores the application of model-informed drug development (MIDD) in the development of a sustained release formulation of flucytosine for cryptococcal meningoencephalitis patients with HIV. It highlights the use of physiologically based pharmacokinetic (PBPK) and biopharmaceutics modeling (PBBM) to optimize therapeutic strategies. Initial PBPK models, based on limited data, were refined using data from Phase 1 studies, enhancing model reliability. The PBPK/PBBM model guided design of a sustained release prototype, dose selection, and dosage determination for a Phase 2 study. MIDD's flexibility allowed for quick assessments of ancillary questions, such as loading dose strategies and drug exposure in unconscious patients. The study underscores the benefits of MIDD in drug development, facilitating informed decisions and optimizing therapeutic outcomes.
