Development and validation of a juvenile porcine model to study antibiotic tissue pharmacokinetics in pediatric sepsis.

01 November 2019 → 31 October 2023
Research Foundation - Flanders (FWO)
Research disciplines
  • Medical and health sciences
    • Pediatrics
    • Pharmacokinetics
sepsis juvenile animal model tissue pharmacokinetics antibiotics
Project description

Performing pediatric drug research is extremely challenging. The development of animal models have been encouraged in guidance documents issued by the regulatory agencies. Pigs display a high degree of anatomical and physiological similarity to humans and are propagated as innovative juvenile animal model for reliable prediction of pediatric pharmacokinetic (PK) behavior. Previous research on antibiotic dose optimization in children is based on blood PK data. However, experts agree that blood concentrations may not always adequately predict concentrations in infected tissue, the actual target site for most antibiotics. It is hypothesized that treatment failure in severe sepsis is partly due to subtherapeutic tissue antibiotic concentrations. We aim to investigate the utility of a juvenile pig model to study antibiotic tissue pharmacokinetics in children with sepsis. We will map antibiotic blood and tissue disposition in the (healthy and septic) piglet and validate the piglet model with blood and tissue data from septic children. Piperacillin-tazobactam and meropenem will serve as exemplary compounds. Their concentration in tissue will be measured using microdialysis. Our research has the potential to decrease the number of children to be recruited in pharmaceutical industry-driven clinical trials, especially in those where tissue concentration measurements are required.