Impact of microdosing clinical study — Why necessary and how useful?
Yuichi Sugiyama, Shinji Yamashita
Advanced Drug Delivery Reviews October 14, 2010 DOI: 10.1016/j.addr.2010.09.010 via OpenAlex
Summary
AI-generated from the abstractMicrodose clinical studies, which administer less than 100 μg of a test compound, allow selection of drug candidates with favorable pharmacokinetic profiles in humans while minimizing risk of harmful events. However, the low dose may produce different pharmacokinetic profiles than at therapeutic doses, and no efficacy or safety information is obtained from such studies. Combining microdose study data with physiologically based pharmacokinetic (PBPK) model analysis of in vitro metabolism, transport, and binding enables accurate prediction of therapeutic-dose pharmacokinetics. Positron emission tomography molecular imaging can further provide efficacy and safety information. Coordinating these methodologies is expected to innovate drug discovery and development.
Study at a glance
| Characteristics | Review Peer reviewed |
|---|---|
| Dose | less than 100 μg |
| Keywords | Microdose Drug development Clinical trial Drug discovery Clinical pharmacology |
| Citations | 60 |
| Key finding | Microdose clinical studies combined with PBPK modeling and PET imaging can improve drug candidate selection and predict therapeutic-dose pharmacokinetics. |
Abstract
The microdose (MD) clinical study enables to select a "better" compound for new drug candidate that shows desirable PK profiles in human. This new methodology is highly expected to streamline the drug development and to increase the success probability in the clinical trial. Since only a small amount of the test compound (less than 100 μg) is administered, the risk of harmful events to a human subject is regarded as minimal in the MD clinical study. However, the low dose also incurs the arguments about the usefulness of this method, since it may result in different PK profiles of drugs from that at the therapeutic dose. In addition, information on the efficacy/safety of the test compound cannot be obtained from the MD clinical study. On the other hand, PBPK model analysis based on the data of both the MD clinical study and in vitro study on metabolism, transport and binding enables the accurate prediction of PK profiles in humans at the therapeutic dose. PET molecular imaging technology further enhances the usability and applicability of the MD clinical study by offering the information on efficacy/safety. These methodologies, if coordinated effectively, are expected to innovate the new drug discovery and development.