Smarter candidate selection--utilizing microdosing in exploratory clinical studies

Microdosing offers a faster and potentially less expensive approach to obtaining human in vivo PK data in early clinical drug development. It encompasses the use of pharmacologically inactive doses of test drug in the low microgram range along with ultrasensitive assay methods (PET, AMS) to assess human exposure in order to extrapolate the PK of higher, clinically more relevant doses, assuming linear PK. This strategy allows early evaluation of systemic clearance, oral bioavailability as well as sources of intersubject variability and questions of specific metabolite formation. It does take advantage of reduced regulatory requirements of preclinical safety studies, bulk drug synthesis (CMC requirements) and easier formulation options, e.g., as part of an exploratory IND; however, this is counterbalanced by a need to synthesize radiolabeled test compound and the development of a sophisticated analytical method. Ongoing studies will determine the predictability of human PK using Microdosing methods.