Modelgebaseerde exploratie van dosisoptimalisatiestrategieën voor vancomycine, meropenem en amikacine in geselecteerde patiëntpopulaties

Optimizing antibiotic therapy in special patient populations (e.g., older adults, critically ill patients with preserved or augmented renal clearance (ARC) admitted to the intensive care unit (ICU), and critically ill adults admitted to the emergency department (ED), is challenging. These special patient populations experience unique (patho-)physiological changes that may lead to suboptimal drug exposure, making the one‑size-fits-all standard dosing strategies inappropriate. Their underrepresentation in clinical trials further limits the available evidence and contributes to uncertainty in dose selection. Pharmacometrics is a discipline that quantify and predict pharmacokinetics (PK) (-pharmacodynamics [PD]) in special patient populations using mathematical models that support data-driven decision-making in clinical research and drug development. Such models enable dose optimization through model-informed precision dosing (MIPD) or dosing simulations. The aim of this doctoral thesis was to explore the value of population PK (popPK) modeling, simulation, and MIPD in optimizing dosing strategies in special patient populations on intravenously administered antibiotics primarily eliminated by the kidneys and been in the market for decades. We hypothesized that applying modeling, simulations, and MIPD in these populations would improve probability of target attainment (PTA), minimize toxicity, and ultimately enhance clinical outcomes.