Microdosing and Other Phase 0 Clinical Trials [electronic resource] : Facilitating Translation in Drug Development
- Washington, D.C. : United States. Dept. of Energy. Office of Science, 2016.
Oak Ridge, Tenn. : Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy
- Physical Description:
- pages 74-88 : digital, PDF file
- Additional Creators:
- Oak Ridge Institute for Science and Education
United States. Department of Energy. Office of Science
United States. Department of Energy. Office of Scientific and Technical Information
- 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. Lastly, 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.
- Published through SciTech Connect.
Clinical and Translational Science 9 2 ISSN 1752-8054 AM
T. Burt; K. Yoshida; G. Lappin; L. Vuong; C. John; SN de Wildt; Y. Sugiyama; M. Rowland.
Netherlands Organisation for Health Research (ZonMw)
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