Pharmacokinetics II: 14C-Labelled Microdosing in Assessing Drug Pharmacokinetics at Phase 0
July 30, 2010 DOI: 10.1007/978-3-7091-0144-5_11 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review |
|---|---|
| Topics | Microdosing |
| Key findings | Microdose pharmacokinetics scale to therapeutic doses within a factor of two for 84% of orally administered drugs and 100% of intravenously administered drugs, based on 23 drugs with comparable data. Non-linearity is interpreted through mechanistic understanding, and 14C labeling facilitates sensitive analysis and early metabolism assessment. |
Abstract
Microdosing came onto the scene with the first publication of data in 2003. Since this time the number of compounds where the pharmacokinetics observed at a microdose compared to a therapeutic dose has grown steadily. Based on current data in the public domain, there are 23 drugs where microdose and therapeutic dose pharmacokinetics can be compared. Of these, 84% scale within a factor of 2 for oral administration and 100% for intravenous administration. Where pharmacokinetic non-linearity is seen, a growing understanding of the mechanisms involved are being applied to interpret the microdose data in the context of the selection of candidate drugs for further development. Inclusion of a 14C isotopic tracer into the molecule enables sensitive AMS analysis to be used as well as obtaining an early indication of the drug’s metabolism in humans.