The Use of Microdosing in the Development of Small Organic and Protein Therapeutics
Journal of Nuclear Medicine May 25, 2017 DOI: 10.2967/jnumed.116.188037 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Microdosing |
| Keywords | Pharmacology Drug development Pharmacokinetics Small molecule |
| Citations | 31 |
| Key findings | Microdosing can accelerate early human studies with reduced preclinical testing, but careful attention is needed to extrapolate low-dose findings to therapeutic doses. |
Abstract
Microdosing as a regulatory concept was introduced to facilitate exploratory studies in humans. The concept involves the use of very low doses of a radionuclide-labeled compound for imaging studies or for assessing plasma pharmacokinetics using equipment that has a highly sensitive readout. The supporting principle is that use of these low doses for a limited time in well-controlled, small populations will limit exposure and have a low risk of adverse effects. Microdosing regulations specify a reduced preclinical toxicology-assessment package in order to shorten the route to human studies and reduce its cost. However, for extrapolation to therapeutically relevant doses and plasma concentrations, there are specific aspects of the use of these low doses and low plasma concentrations that require special attention. These specific aspects are reviewed in this article, with separate attention being paid to small organic molecules and protein therapeutics. The indications for microdosing in drug development are discussed in terms of the 3 pillars of survival in drug development, the first of which is characterization of tissue distribution and access to the site of action; the second, engagement of the target; and the third, induction of tissue responses relevant to a therapeutic response.
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 | |
| Microdosing and Other Phase 0 Clinical Trials: Facilitating Translation in Drug Development | 2016 | Review | |
| Expectancy Effects in Psychedelic Trials. | 2024 | Review |
Citations in the library
Cites 5
- Positron emission tomography microdosing: a new concept with application in tracer and early clinical drug development European Journal of Clinical Pharmacology September 1, 2003
- Use of microdosing to predict pharmacokinetics at the therapeutic dose: Experience with 5 drugs Clinical Pharmacology & Therapeutics September 1, 2006
- Microdosing and drug development: past, present and future Expert Opinion on Drug Metabolism & Toxicology April 4, 2013
- To Apply Microdosing or Not? Recommendations to Single Out Compounds with Non-Linear Pharmacokinetics. Clinical Pharmacokinetics January 2016
- Microdosing in early lead discovery. Bioanalysis March 2010