Microdosing and drug development: past, present and future

Microdosing uses inherently safe, sub-pharmacologic doses of drug to acquire exploratory pharmacokinetic data in humans early in drug development. A decade after the first microdose data publication, evidence suggests microdosing may predict human pharmacokinetics better than alternative methods. Combining microdosing with physiologically based modeling could yield more reliable future predictions. The concept has been applied to drug-drug interactions, polymorphism, and assessing drug concentrations over time at the site of action. Microdosing may offer additional unanticipated benefits not yet fully realized.

Study at a glance

Abstract

INTRODUCTION: Microdosing is an approach to early drug development where exploratory pharmacokinetic data are acquired in humans using inherently safe sub-pharmacologic doses of drug. The first publication of microdose data was 10 years ago and this review comprehensively explores the microdose concept from conception, over the past decade, up until the current date. AREAS COVERED: The authors define and distinguish the concept of microdosing from similar approaches. The authors review the ability of microdosing to provide exploratory pharmacokinetics (concentration-time data) but exclude microdosing using positron emission tomography. The article provides a comprehensive review of data within the peer-reviewed literature as well as the latest applications and a look into the future, towards where microdosing may be headed. EXPERT OPINION: Evidence so far suggests that microdosing may be a better predictive tool of human pharmacokinetics than alternative methods and combination with physiologically based modelling may lead to much more reliable predictions in the future. The concept has also been applied to drug-drug interactions, polymorphism and assessing drug concentrations over time at its site of action. Microdosing may yet have more to offer in unanticipated directions and provide benefits that have not been fully realised to date.