Human microdosing (Human Phase 0) is a relatively new concept, which relies on the ultrasensitivity of accelerator mass spectrometry (AMS). It is now possible to conduct a full human metabolism study after administration of as little as 0.5 microgram of drug substance.
Speaking at the recent Global Pharma R&D Summit held in Anaheim, California, Andrew von Eschenbach. Acting Commissioner of the US FDA, said: "Phase 0 studies are an extremely important mechanism to reduce risk for drug developers. I would encourage innovators to take more risk in exploring this approach."
He added: "I think the cancer community in particular should be adopting Phase 0 studies."
In microdosing one or more drug candidates are taken into humans at trace doses in order to obtain early ADME and PK information. This information is then used as part of the decision tree to select which of the microdosed drugs has the appropriate PK parameters to take further.
The aim of these low dose screening ADME studies is to ensure that drugs do not have to be dropped later down the development pathway because of inappropriate metabolism eg first pass, too short a half-life, poor bioavailability etc.
As many as one drug in three will be dropped at the Phase I stage of drug development because of PK, pharmacodynamic or toxicity issues. Human microdosing aims to reduce attrition at Phase I.
As recently demonstrated by the publication of the results of the independent CREAM trial microdosing provides an insight into the human pharmacokinetics (PK) of new drug candidates.
This can then be used to assist in the compound candidate selection process, as well as help establish the likely pharmacological dose and thereby determine the first dose for the subsequent Phase I study.
Working on the principle that 'the best model for humans is human', human microdosing, using Accelerator Mass Spectrometry, enables the introduction of sub-pharmacological doses of new drugs into man much earlier than ever before possible
Other advantages to microdosing include the ability to select the best animal species for long-term toxicological studies from microdose metabolite profiling data and allowing cost analysis of goods when the drug goes into production.