Microdosing and Other Phase 0 Clinical Trials: Facilitating Translation in Drug Development
Tal Burt, K Yoshida, Graham Lappin, L Vuong, C John, SN De Wildt, Yuichi Sugiyama, M Rowland
Clinical and Translational Science February 26, 2016 DOI: 10.1111/cts.12390 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Microdosing |
| Citations | 91 |
| Key findings | Argues that microdosing and other phase 0 approaches will be increasingly used in drug development because of rising costs and ethical concerns about exposing humans and animals to novel compounds, and that growing evidence supports extrapolating from limited drug exposure to full therapeutic exposure. Contends these approaches offer versatility across pharmacokinetic, bioavailability, drug-drug interaction, and mechanistic pharmacodynamic studies, including PET microdosing and Intra-Target Microdosing (ITM), and may be valuable in vulnerable populations and extreme environments. |
Abstract
A number of drivers and developments suggest that microdosing and other phase 0 applications will experience increased utilization in the near-to-medium future. Increasing costs of drug development and ethical concerns about the risks of exposing humans and animals to novel chemical entities are important drivers in favor of these approaches, and can be expected only to increase in their relevance. An increasing body of research supports the validity of extrapolation from the limited drug exposure of phase 0 approaches to the full, therapeutic exposure, with modeling and simulations capable of extrapolating even non-linear scenarios. An increasing number of applications and design options demonstrate the versatility and flexibility these approaches offer to drug developers including the study of PK, bioavailability, DDI, and mechanistic PD effects. PET microdosing allows study of target localization, PK and receptor binding and occupancy, while Intra-Target Microdosing (ITM) allows study of local therapeutic-level acute PD coupled with systemic microdose-level exposure. Applications in vulnerable populations and extreme environments are attractive due to the unique risks of pharmacotherapy and increasing unmet healthcare needs. All phase 0 approaches depend on the validity of extrapolation from the limited-exposure scenario to the full exposure of therapeutic intent, but in the final analysis the potential for controlled human data to reduce uncertainty about drug properties is bound to be a valuable addition to the drug development process.
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 | |
| Phase 0/microdosing approaches: time for mainstream application in drug development? | 2020 | Review | |
| Microdosing and drug development: past, present and future | 2013 | 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 9
- Phase 0/microdosing approaches: time for mainstream application in drug development? Nature Reviews Drug Discovery September 8, 2020
- Potential safety, benefits, and influence of the placebo effect in microdosing psychedelic drugs: A systematic review Neuroscience & Biobehavioral Reviews October 5, 2020
- PK and PK / PD Modeling of Bcl2 Inhibitor S65487 in Patients With AML and Investigation of Nonlinearity With Microdosing CPT: Pharmacometrics & Systems Pharmacology June 17, 2026
- 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
and 4 more in the library
Cites 17
- 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 12 more in the library