Early clinical drug development has seen little change in 20 years despite a 40% failure rate due to poor drug metabolism and pharmacokinetics. A new method called microdosing allows investigational drugs to be tested in humans earlier, enabling smarter candidate selection. Microdosing relies on two ultrasensitive techniques: positron emission tomography (PET) for pharmacodynamic information and accelerator mass spectrometry (AMS) for pharmacokinetic information. This approach permits safer human studies and reduces the use of animals in preclinical toxicology.
Microdosing Phase 0 studies provide early information about a drug's pharmacokinetics and limited pharmacodynamics before expensive Phase I trials. Developed in the 2000s, this method helps select drug candidates and uses ultrasensitive accelerator mass spectrometry. The chapter reviews the scientific, regulatory, ethical, and commercial aspects of microdosing, arguing that because the best model for humans is human, microdose studies should replace early in vitro and preclinical work as more relevant and predictive of a drug's ADME at therapeutic doses, offering a new paradigm for early drug development.