The expanding utility of microdosing

Area of Science:

• Pharmacokinetics and Drug Development
• Translational Medicine

Background:

• Microdosing, the administration of sub-pharmacologic drug doses (≤100 µg or 1% of pharmacologic dose), has been utilized for over a decade.
• A primary concern has been the potential for nonlinear pharmacokinetics (PK) between microdoses and therapeutic doses.

Purpose of the Study:

• To evaluate the utility and emerging applications of microdosing in drug development.
• To assess the predictability of human pharmacokinetics (PK) using microdosing compared to other predictive methods.

Main Methods:

• Sub-pharmacologic administration of investigational drugs to human subjects to determine pre-Phase 1 PK.
• Development of methods to assess the potential for nonlinear PK prior to study initiation.

Main Results:

• Approximately 80% of orally administered drugs and 100% of intravenously administered drugs exhibit scalable PK (within a factor of 2) between microdoses and therapeutic doses.
• Microdosing has demonstrated utility in pediatrics, protein therapeutics, and intra-arterial applications focusing on localized pharmacodynamics.

Conclusions:

• Microdosing offers a valuable tool for understanding PK before Phase 1 clinical trials, outperforming other predictive methods like PBPK modeling and allometry.
• Despite a currently limited database, microdosing provides significant insights into drug behavior in humans, with emerging techniques addressing previous limitations.