The application of Phase 0 and microtracer approaches in early clinical development: past, present, and future
Phase 0 microdosing studies were introduced to the drug development community approximately 20 years ago. A microdose is defined as less than 1/100th of the dose calculated based on animal data to yield a pharmacological effect in humans, with a maximum of 100 μg, or 30 nmoles for protein products....
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1369079/full |
| _version_ | 1797258592904019968 |
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| author | A. F. Roffel E.-J. van Hoogdalem |
| author_facet | A. F. Roffel E.-J. van Hoogdalem |
| author_sort | A. F. Roffel |
| collection | DOAJ |
| description | Phase 0 microdosing studies were introduced to the drug development community approximately 20 years ago. A microdose is defined as less than 1/100th of the dose calculated based on animal data to yield a pharmacological effect in humans, with a maximum of 100 μg, or 30 nmoles for protein products. In our experience, Phase 0 microdose studies have not been fully embraced by the pharmaceutical industry. This notion is based on the number of Phase 0 studies that we have been involved in. Thus, we conducted at least 17 Phase 0 microdose studies in the Zero’s (on average, two per year), but in the years beyond this, it was only 15 studies (1.4 per year); in these latter years, we did conduct a total of 23 studies which employed an intravenous (i.v.) microdose for absolute bioavailability (ABA) assessments (two per year on average), which are the most used and potentially informative type of clinical study using a microdose, albeit they are formally not microdose studies. In the current review, we summarize the past use of and experience with Phase 0 microdose designs in early clinical development, including intravenous 14C microdose ABA studies, and assess what is needed to increase the adoption of useful applications of Phase 0/microdose studies in the near future. |
| first_indexed | 2024-04-24T22:55:59Z |
| format | Article |
| id | doaj.art-6c355cef4c7f46e4b9e58f9329243ad2 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-24T22:55:59Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-6c355cef4c7f46e4b9e58f9329243ad22024-03-18T04:49:21ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-03-011510.3389/fphar.2024.13690791369079The application of Phase 0 and microtracer approaches in early clinical development: past, present, and futureA. F. RoffelE.-J. van HoogdalemPhase 0 microdosing studies were introduced to the drug development community approximately 20 years ago. A microdose is defined as less than 1/100th of the dose calculated based on animal data to yield a pharmacological effect in humans, with a maximum of 100 μg, or 30 nmoles for protein products. In our experience, Phase 0 microdose studies have not been fully embraced by the pharmaceutical industry. This notion is based on the number of Phase 0 studies that we have been involved in. Thus, we conducted at least 17 Phase 0 microdose studies in the Zero’s (on average, two per year), but in the years beyond this, it was only 15 studies (1.4 per year); in these latter years, we did conduct a total of 23 studies which employed an intravenous (i.v.) microdose for absolute bioavailability (ABA) assessments (two per year on average), which are the most used and potentially informative type of clinical study using a microdose, albeit they are formally not microdose studies. In the current review, we summarize the past use of and experience with Phase 0 microdose designs in early clinical development, including intravenous 14C microdose ABA studies, and assess what is needed to increase the adoption of useful applications of Phase 0/microdose studies in the near future.https://www.frontiersin.org/articles/10.3389/fphar.2024.1369079/fullPhase 0microdosingdrug discovery and developmentexploratory clinical trialsGMP |
| spellingShingle | A. F. Roffel E.-J. van Hoogdalem The application of Phase 0 and microtracer approaches in early clinical development: past, present, and future Frontiers in Pharmacology Phase 0 microdosing drug discovery and development exploratory clinical trials GMP |
| title | The application of Phase 0 and microtracer approaches in early clinical development: past, present, and future |
| title_full | The application of Phase 0 and microtracer approaches in early clinical development: past, present, and future |
| title_fullStr | The application of Phase 0 and microtracer approaches in early clinical development: past, present, and future |
| title_full_unstemmed | The application of Phase 0 and microtracer approaches in early clinical development: past, present, and future |
| title_short | The application of Phase 0 and microtracer approaches in early clinical development: past, present, and future |
| title_sort | application of phase 0 and microtracer approaches in early clinical development past present and future |
| topic | Phase 0 microdosing drug discovery and development exploratory clinical trials GMP |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1369079/full |
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