Phase 0 approaches, including microdosing, are early-stage clinical trials that test very low, subtherapeutic doses of new drugs in humans to gather safety and pharmacological data before larger studies. Traditionally used to assess pharmacokinetics, these methods now also help understand a drug's mechanism of action and pharmacodynamics. Phase 0 trials can improve the selection of drug candidates for further development, making the process safer, cheaper, quicker, and more informed. While challenges like extrapolating results to therapeutic doses and managing development timelines remain, the authors suggest that phase 0 approaches should be considered for most drug development scenarios.
Microdosing uses inherently safe, sub-pharmacologic doses of drug to acquire exploratory pharmacokinetic data in humans early in drug development. A decade after the first microdose data publication, evidence suggests microdosing may predict human pharmacokinetics better than alternative methods. Combining microdosing with physiologically based modeling could yield more reliable future predictions. The concept has been applied to drug-drug interactions, polymorphism, and assessing drug concentrations over time at the site of action. Microdosing may offer additional unanticipated benefits not yet fully realized.