Nature Reviews Drug Discovery
September 8, 2020
Tal Burt, Graeme Young, Wooin Lee et al.
101 citations
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.
Drugs in R&D
January 1, 2008
Martin Bauer, Cláudia Wagner, Oliver Langer
52 citations
Positron emission tomography (PET)-microdosing involves giving human subjects a carbon-11- or fluorine-18-labeled drug candidate in microgram amounts to track the drug's concentration over time in targeted body tissues. Because only tiny amounts of unlabeled drug are used, toxicological risk is very low, and regulatory authorities require less preclinical safety testing than for conventional phase 1 studies. Microdose studies are becoming more important in clinical drug research because they can shorten development timelines and reduce costs. The review covers current PET applications in anticancer, anti-infective, and central nervous system drug research.
Drug metabolism and disposition: the biological fate of chemicals
July 1, 2025
Severin Mairinger, Mihye Kwon, Martin Bauer et al.
Systemic absorption of a topically applied drug may not be dose-linear, limiting the usefulness of microdosing to predict therapeutic-dose exposure. In a crossover study of eight healthy participants, a topical microdose of diclofenac (62 μg) resulted in a higher fraction absorbed (0.48%) compared with a therapeutic dose (120 mg, 0.13%), a 3.79-fold difference. Intravenous dosing showed dose-linear disposition. Concentrations in subcutaneous tissue microdialysates were low and variable regardless of dose. The findings indicate that microdosing may not accurately predict the systemic availability of certain topical drugs at therapeutic doses.