Status: Funded - Open
Use of physiologically-based pharmacokinetic models to streamline pediatric drug approvals
Daniel Gonzalez, Pharm.D., Ph.D.
BACKGROUND: Antibiotics are the mainstay of therapy for invasive infections; however, in the last decade only 3 new antibiotics were approved by the FDA, none of which are approved in children.
GAP: This proposal will evaluate a platform to systematically develop and validate physiologically-based PK (PBPK) models in adults and children to shorten the time to pediatric antibiotic approval early in drug development.
HYPOTHESIS: Using solithromycin as a probe drug, we will test two hypotheses: 1) a PBPK model will successfully predict 90% of the observed adult plasma and bronchial fluid concentrations; 2) accounting for growth and maturation, the pediatric PBPK model and dose adjustments will predict drug exposure in plasma and bronchial fluid within ±15% of exposures observed in adults.
METHODS: We will develop an adult PBPK model, which will be scaled to children, and then validated using available clinical data.
IMPACT: This systematic approach could be applied to future pediatric drug development programs.
University of North Carolina