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Updated: Jan 25, 2026
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An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
Published on: December 3, 2020
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Predictive Value of Microdose Pharmacokinetics
Merel van Nuland1,2, Hilde Rosing3, Alwin D R Huitema3,4,5
1Department of Pharmacy and Pharmacology, Antoni van Leeuwenhoek-The Netherlands Cancer Institute, Louwesweg 6, 1066 EC, Amsterdam, The Netherlands. m.v.nuland@nki.nl.
Clinical Pharmacokinetics
|April 29, 2019
Summary
Phase 0 microdose trials show good predictability for drug pharmacokinetics. These early studies effectively model human drug behavior, aiding in the development of new chemical entities.
Area of Science:
- Pharmacology
- Drug Development
- Clinical Trials
Background:
- Phase 0 microdose trials assess early human pharmacokinetics of new chemical entities.
- These studies aim to limit participant exposure and risks.
- A key assumption is that microdose pharmacokinetics predict therapeutic dose pharmacokinetics.
Purpose of the Study:
- To evaluate the predictive accuracy of microdose pharmacokinetics.
- To identify drug characteristics influencing the scalability of pharmacokinetic parameters.
- To determine if microdose studies are reliable indicators of later-stage drug behavior.
Main Methods:
- Reviewed 46 compounds to assess microdose pharmacokinetic predictability.
- Defined adequate predictability as microdose and therapeutic dose values within twofold.
- Analyzed potential causes of pharmacokinetic nonlinearity, such as enzyme and transporter saturation.
Main Results:
- Microdose pharmacokinetics demonstrated adequate predictability for 68% of orally administered drugs (28/41).
- Predictability was higher for intravenously administered drugs, with 94% (15/16) showing adequate prediction.
- Linear pharmacokinetics were successfully predicted in a high proportion of cases.
Conclusions:
- Phase 0 microdose trials offer valuable early human pharmacokinetic data.
- These trials can serve as an effective model for determining drug pharmacokinetics.
- The findings support the utility of microdosing in early drug development for predicting in vivo behavior.
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