ABSTRACT
One of the most challenging aspects of drug development is the design of the initial
clinical protocol, especially the selection of the starting dose for a first-in-human
(FIH) trial. For a typical investigational new drug application (IND), selection of
the starting dose for the FIH trial, by its very nature, is based solely on non-clinical
data (usually in at least two animal species) and, perhaps, in vitro metabolism data
in human liver microsomes (or hepatocytes). Although the selection of a safe
starting dose is relatively easy, in that one can always pick a very low dose
relative to doses used in the animal toxicity studies, the challenge is to select a
dose that is safe, but not so low as to result in an unreasonable amount of time
being taken to achieve doses that are anticipated to be therapeutically relevant.
