Phase 0 trials/ Intra-Target-Microdosing (ITM) and the lung: a review
BMC Pulmonary Medicine September 1, 2024 Tom M. Quinn, Annya M. Bruce, Tal Burt et al.
Phase 0 trials, positioned between preclinical research and phase I, test sub-clinical microdoses in humans to gather early pharmacokinetic, pharmacodynamic, and mechanistic data, improving drug development efficiency and reducing animal testing. Traditional phase 0 trials use sub-therapeutic microdoses administered intravenously, with readouts from accelerator mass spectrometry, liquid chromatography tandem mass spectrometry, and whole-body positron emission tomography. Mathematical models extrapolate pharmacokinetic data for larger doses but are limited for pharmacodynamic and target engagement data. An Intra-Target Microdosing approach exposes a small body compartment to potentially clinically active local concentrations, enabling pharmacodynamic data collection and target engagement evidence, with potential for rapid, cost-effective development of new and repurposed drugs in the pulmonary system.