Physiologically-based pharmacokinetic modelling in sepsis; a tool to elucidate how pathophysiology affects meropenem pharmacokinetics

Applying physiologically-based pharmacokinetic (PBPK) modelling in sepsis could help to better understand how PK changes are influenced by drug- and patient-related factors. We aimed to elucidate the influence of sepsis pathophysiology on the PK of meropenem by applying PBPK modelling. A whole-body meropenem PBPK model was developed and evaluated in healthy individuals, and renally impaired non-septic patients. Sepsis-induced physiological changes in body composition, organ blood flow, kidney function, albumin, and haematocrit were implemented according to a previously proposed PBPK sepsis model. Model performance was evaluated, and a local sensitivity analysis was conducted. The model-predicted PK metrics (AUC, C