Microdosing: a critical assessment of human data

Ultrasensitive analytical methodologies have now made possible the ability to characterize the pharmacokinetics (PK) of compounds following administration to humans of a minute, subpharmacologic dose, a microdose. This has the potential to provide pre-IND information to help in early candidate selection, but only if such information is reasonably predictive of PK at pharmacologic doses. The published clinical data in this area are critically assessed and perspectives drawn. The place of microdosing, alone and coupled with other innovative methodologies, both pre-IND and during clinical development, is considered as a way forward to improve the efficiency and informativeness of drug development.