Phase 0/microdosing approaches: time for mainstream application in drug development?
Tal Burt, Graeme C. Young, Wooin Lee, Hiroyuki Kusuhara, Oliver Langer, Malcolm Rowland, Yuichi Sugiyama
Nature Reviews Drug Discovery September 8, 2020 DOI: 10.1038/s41573-020-0080-x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Microdosing |
| Keywords | Mainstream Drug development Pharmacology |
| Citations | 101 |
| Key findings | Phase 0 approaches can improve preclinical candidate selection and enable safer, cheaper, quicker, and more informed developmental decisions. |
Abstract
Phase 0 approaches - which include microdosing - evaluate subtherapeutic exposures of new drugs in first-in-human studies known as exploratory clinical trials. Recent progress extends phase 0 benefits beyond assessment of pharmacokinetics to include understanding of mechanism of action and pharmacodynamics. Phase 0 approaches have the potential to improve preclinical candidate selection and enable safer, cheaper, quicker and more informed developmental decisions. Here, we discuss phase 0 methods and applications, highlight their advantages over traditional strategies and address concerns related to extrapolation and developmental timelines. Although challenges remain, we propose that phase 0 approaches be at least considered for application in most drug development scenarios.
Comparable studies
Other narrative reviews on microdosing, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Big physics, small doses: the use of AMS and PET in human microdosing of development drugs | 2003 | Review | |
| Microdosing and drug development: past, present and future | 2013 | Review | |
| Microdosing and Other Phase 0 Clinical Trials: Facilitating Translation in Drug Development | 2016 | Review | |
| Expectancy Effects in Psychedelic Trials. | 2024 | Review | |
| Impact of microdosing clinical study — Why necessary and how useful? | 2010 | Review |
Citations in the library
Cited by 7
- Modeling Whole-Body Dynamic PET Microdosing Data to Predict the Whole-Body Pharmacokinetics of Glyburide in Humans. Clinical Pharmacokinetics November 1, 2025
- Evaluation of dose linearity in the systemic availability and pharmacokinetics of topically administered diclofenac: A 14C-microdosing study in healthy volunteers. Drug Metabolism and Disposition July 1, 2025
- Phase 0 trials/ Intra-Target-Microdosing (ITM) and the lung: a review BMC Pulmonary Medicine September 1, 2024
- When to consider intra-target microdosing: physiologically based pharmacokinetic modeling approach to quantitatively identify key factors for observing target engagement Frontiers in Pharmacology July 25, 2024
- Editorial: Incorporating Phase 0 microdosing as a powerful tool into a new vision of drug development Frontiers in Pharmacology July 16, 2024
and 2 more in the library
Cites 31
- Positron emission tomography microdosing: a new concept with application in tracer and early clinical drug development European Journal of Clinical Pharmacology September 1, 2003
- Big physics, small doses: the use of AMS and PET in human microdosing of development drugs Nature Reviews Drug Discovery February 28, 2003
- Use of microdosing to predict pharmacokinetics at the therapeutic dose: Experience with 5 drugs Clinical Pharmacology & Therapeutics September 1, 2006
- Identification of the Rate-Determining Process in the Hepatic Clearance of Atorvastatin in a Clinical Cassette Microdosing Study Clinical Pharmacology & Therapeutics August 10, 2011
- Microdosing Clinical Study: Pharmacokinetic, Pharmacogenomic (SLCO2B1), and Interaction (Grapefruit Juice) Profiles of Celiprolol Following the Oral Microdose and Therapeutic Dose The Journal of Clinical Pharmacology May 19, 2011
and 26 more in the library